Phosphinate ruthenium complexes

ABSTRACT

Provided herein are ruthenium complexes of Formula (I), and processes of preparation thereof. Also provided are methods of their use as a metathesis catalyst.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a 371 of International Patent Application No.PCT/US2010/022798, filed on Feb. 2, 2010, which claims priority to U.S.Provisional Application Nos. 61/149,662, filed Feb. 3, 2009, and61/231,408, filed Aug. 5, 2009, the disclosure of each of which isincorporated herein by reference in its entirety.

FIELD

Provided herein are ruthenium complexes, and processes of preparationthereof. Also provided are methods of their use as a metathesiscatalyst.

BACKGROUND

Olefin metathesis provides an efficient method for the construction ofcarbon-carbon double bonds and has emerged as a powerful tool inpreparation of cyclic organic molecules and polymeric materials. Somecommon olefin metathesis reactions include ring closure metathesis(RCM), acyclic diene metathesis polymerization (ADMET), ring openingmetathesis polymerization (ROMP), ring opening metathesis (ROM), andcross metathesis (CM).

In recent years, olefin metathesis has been increasingly used by thepharmaceutical industry to synthesize biologically active molecules(Wallace et al., “A Double Ring Closing Metathesis Reaction in theRapid, Enantioselective Synthesis of NK-1 Receptor Antagonists,” Org.Lett. 2001, 3, 671-674; Kanada et al., “Total Synthesis of the PotentAntitumor macrolides Pladienolide B and D,” Angew. Chem., Int. Ed. 2007,46, 4350-4355). The increasing use of olefin metathesis inpharmaceutical industry has increased the demand for more efficientolefin metathesis catalysts.

SUMMARY OF THE DISCLOSURE

Provided herein is a ruthenium complex of Formula I:

wherein:

L is a neutral ligand;

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ Cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

X¹ and X² are each independently an anionic ligand;

Y is a bond or —NR^(b)—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

Also provided herein is a ruthenium complex of Formula I:

wherein:

L is a neutral ligand;

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

X¹ and X² are each independently an anionic ligand;

Y is a bond or —NR^(b)—;

Z is O or S;

n is an integer of 0, 1, 2, or 3;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; and

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —S(O)R^(e), —S(O)₂R^(e), or —S(O)₂NR^(f)R^(g);wherein each R^(e), R^(f), R^(g), and R^(h) is independently hydrogen;C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; or R^(f) and R^(g) togetherwith the N atom to which they are attached form heterocyclyl.

Further provided herein is a compound of Formula II:

wherein:

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c).

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

-   -   each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl,        C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,        heteroaryl, or heterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

Y is a bond or —NR^(b)—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OC(O)R^(a), —OC(O)OR^(a), —OC(O)NR^(b)R^(c),—OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a), —OS(O)NR^(b)R^(c),—OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d), —NR^(a)C(O)OR^(d),—NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c), —NR^(a)S(O)R^(d),—NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c), —NR^(a)S(O)₂NR^(b)R^(c),—PR^(a)R^(d), —P(OR^(a))R^(d), —P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d),—P(O)(OR^(a))R^(d), —P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a),—S(O)₂R^(a), or —SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), andR^(d) is independently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl,each optionally substituted with one or more, in one embodiment, one,two, three, or four, substituents Q; or R^(b) and R^(c) together withthe N atom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

Provided herein is a compound of Formula II:

wherein:

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3h)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

Y is a bond or —NR^(b)—;

Z is O or S;

n is an integer of 0, 1, 2, or 3;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; and

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —R^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —S(O)R^(e), —S(O)₂R^(e), or —S(O)₂NR^(f)R^(g);wherein each R^(e), R^(f), R^(g), and R^(h) is independently hydrogen;C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; or R^(f) and R^(g) togetherwith the N atom to which they are attached form heterocyclyl.

Furthermore, provided herein is a method for catalyzing an olefinmetathesis reaction, comprising the step of contacting an olefin with aruthenium complex of Formula I.

Also provided herein is a method for catalyzing a ring closuremetathesis, comprising the step of contacting a compound having two ormore olefin groups with a ruthenium complex of Formula I.

DETAILED DESCRIPTION

To facilitate understanding of the disclosure set forth herein, a numberof terms are defined below.

Generally, the nomenclature used herein and the laboratory procedures inchemistry described herein are those well known and commonly employed inthe art. Unless defined otherwise, all technical and scientific termsused herein generally have the same meaning as commonly understood byone of ordinary skill in the art to which this disclosure belongs.

The term “alkyl” refers to a linear or branched saturated monovalenthydrocarbon radical, wherein the alkyl may optionally be substituted asdescribed herein. For example, C₁₋₆ alkyl refers to a linear saturatedmonovalent hydrocarbon radical of 1 to 6 carbon atoms or a branchedsaturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. Incertain embodiments, the alkyl is a linear saturated monovalenthydrocarbon radical that has 1 to 20 (C₁₋₂₀), 1 to 15 (C₁₋₁₅), 1 to 10(C₁₋₁₀), or 1 to 6 (C₁₋₆) carbon atoms, or branched saturated monovalenthydrocarbon radical of 3 to 20 (C₃₋₂₀), 3 to 15 (C₃₋₁₅), 3 to 10(C₃₋₁₀), or 3 to 6 (C₃₋₆) carbon atoms. As used herein, linear C₁₋₆ andbranched C₃₋₆ alkyl groups are also referred as “lower alkyl.” Examplesof alkyl groups include, but are not limited to, methyl, ethyl, propyl(including all isomeric forms), n-propyl, isopropyl, butyl (includingall isomeric forms), n-butyl, isobutyl, sec-butyl, t-butyl, pentyl(including all isomeric forms), and hexyl (including all isomericforms).

The term “alkenyl” refers to a linear or branched monovalent hydrocarbonradical, which contains one or more, in one embodiment, one to five, inanother embodiment, one, carbon-carbon double bond(s). The alkenyl maybe optionally substituted as described herein. The term “alkenyl”embraces radicals having a “cis” or “trans” configuration or a mixturethereof, or alternatively, a “Z” or “E” configuration or a mixturethereof, as appreciated by those of ordinary skill in the art. Forexample, C₂₋₆ alkenyl refers to a linear unsaturated monovalenthydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturatedmonovalent hydrocarbon radical of 3 to 6 carbon atoms. In certainembodiments, the alkenyl is a linear monovalent hydrocarbon radical of 2to 20 (C₂₋₂₀), 2 to 15 (C₂₋₁₅), 2 to 10 (C₂₋₁₀), or 2 to 6 (C₂₋₆) carbonatoms, or a branched monovalent hydrocarbon radical of 3 to 20 (C₃₋₂₀),3 to 15 (C₃₋₁₅), 3 to 10 (C₃₋₁₀), or 3 to 6 (C₃₋₆) carbon atoms.Examples of alkenyl groups include, but are not limited to, ethenyl,propen-1-yl, propen-2-yl, allyl, butenyl, and 4-methylbutenyl.

The term “alkynyl” refers to a linear or branched monovalent hydrocarbonradical, which contains one or more, in one embodiment, one to five, inanother embodiment, one, carbon-carbon triple bond(s). The alkynyl maybe optionally substituted as described herein. For example, C₂₋₆ alkynylrefers to a linear unsaturated monovalent hydrocarbon radical of 2 to 6carbon atoms or a branched unsaturated monovalent hydrocarbon radical of3 to 6 carbon atoms. In certain embodiments, the alkynyl is a linearmonovalent hydrocarbon radical of 2 to 20 (C₂₋₂₀), 2 to 15 (C₂₋₁₅), 2 to10 (C₂₋₁₀), or 2 to 6 (C₂₋₆) carbon atoms, or a branched monovalenthydrocarbon radical of 3 to 20 (C₃₋₂₀), 3 to 15 (C₃₋₁₅), 3 to 10(C₃₋₁₀), or 3 to 6 (C₃₋₆) carbon atoms. Examples of alkynyl groupsinclude, but are not limited to, ethynyl (—C≡CH), propynyl (includingall isomeric forms, e.g., 1-propynyl (—C≡CCH₃) and propargyl(—CH₂C≡CH)), butynyl (including all isomeric foams, e.g., 1-butyn-1-yland 2-butyn-1-yl), pentynyl (including all isomeric forms, e.g.,1-pentyn-1-yl and 1-methyl-2-butyn-1-yl), and hexynyl (including allisomeric forms, e.g., 1-hexyn-1-yl).

The term “cycloalkyl” refers to a cyclic monovalent hydrocarbon radical,which may be optionally substituted as described herein. In oneembodiment, cycloalkyl groups may be saturated or unsaturated butnon-aromatic, and/or bridged, and/or non-bridged, and/or fused bicyclicgroups. In certain embodiments, the cycloalkyl has from 3 to 20 (C₃₋₂₀),from 3 to 15 (C₃₋₁₅), from 3 to 10 (C₃₋₁₀), or from 3 to 7 (C₃₋₇) carbonatoms. Examples of cycloalkyl groups include, but are not limited to,cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl,cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl,bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, decalinyl, and adamantyl.

The term “aryl” refers to a monovalent monocyclic aromatic group and/ormonovalent multicyclic aromatic group that contain at least one aromaticcarbon ring. In certain embodiments, the aryl has from 6 to 20 (C₆₋₂₀),from 6 to 15 (C₆₋₁₅), or from 6 to 10 (C₆₋₁₀) ring atoms. Examples ofaryl groups include, but are not limited to, phenyl, naphthyl,fluorenyl, azulenyl, anthryl, phenanthryl, pyrenyl, biphenyl, andterphenyl. Aryl also refers to bicyclic or tricyclic carbon rings, whereone of the rings is aromatic and the others of which may be saturated,partially unsaturated, or aromatic, for example, dihydronaphthyl,indenyl, indanyl, or tetrahydronaphthyl (tetralinyl). In certainembodiments, aryl may be optionally substituted as described herein.

The term “aralkyl” or “arylalkyl” refers to a monovalent alkyl groupsubstituted with one or more aryl groups. In certain embodiments, thearalkyl has from 7 to 30 (C₇₋₃₀), from 7 to 20 (C₇₋₂₀), or from 7 to 16(C₇₋₁₆) carbon atoms. Examples of aralkyl groups include, but are notlimited to, benzyl, 2-phenylethyl, and 3-phenylpropyl. In certainembodiments, aralkyl are optionally substituted with one or moresubstituents as described herein.

The term “heteroaryl” refers to a monovalent monocyclic aromatic groupor monovalent multicyclic aromatic group that contain at least onearomatic ring, wherein at least one aromatic ring contains one or moreheteroatoms independently selected from O, S, and N in the ring.Heteroaryl groups are bonded to the rest of a molecule through thearomatic ring. Each ring of a heteroaryl group can contain one or two Oatoms, one or two S atoms, and/or one to four N atoms, provided that thetotal number of heteroatoms in each ring is four or less and each ringcontains at least one carbon atom. In certain embodiments, theheteroaryl has from 5 to 20, from 5 to 15, or from 5 to 10 ring atoms.Examples of monocyclic heteroaryl groups include, but are not limitedto, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl,oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl,pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl,triazinyl, and triazolyl. Examples of bicyclic heteroaryl groupsinclude, but are not limited to, benzofuranyl, benzimidazolyl,benzoisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl,benzothienyl, benzotriazolyl, benzoxazolyl, furopyridyl,imidazopyridinyl, imidazothiazolyl, indolizinyl, indolyl, indazolyl,isobenzofuranyl, isobenzothienyl, isoindolyl, isoquinolinyl,isothiazolyl, naphthyridinyl, oxazolopyridinyl, phthalazinyl,pteridinyl, purinyl, pyridopyridyl, pyrrolopyridyl, quinolinyl,quinoxalinyl, quinazolinyl, thiadiazolopyrimidyl, and thienopyridyl.Examples of tricyclic heteroaryl groups include, but are not limited to,acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, perimidinyl,phenanthrolinyl, phenanthridinyl, phenarsazinyl, phenazinyl,phenothiazinyl, phenoxazinyl, and xanthenyl. In certain embodiments,heteroaryl may also be optionally substituted as described herein.

The term “heterocyclyl” or “heterocyclic” refers to a monovalentmonocyclic non-aromatic ring system or monovalent multicyclic ringsystem that contains at least one non-aromatic ring, wherein one or moreof the non-aromatic ring atoms are heteroatoms independently selectedfrom O, S, or N; and the remaining ring atoms are carbon atoms. Incertain embodiments, the heterocyclyl or heterocyclic group has from 3to 20, from 3 to 15, from 3 to 10, from 3 to 8, from 4 to 7, or from 5to 6 ring atoms. Heterocyclyl groups are bonded to the rest of amolecule through the non-aromatic ring. In certain embodiments, theheterocyclyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ringsystem, which may be fused or bridged, and in which nitrogen or sulfuratoms may be optionally oxidized, nitrogen atoms may be optionallyquaternized, and some rings may be partially or fully saturated, oraromatic. The heterocyclyl may be attached to the main structure at anyheteroatom or carbon atom which results in the creation of a stablecompound. Examples of such heterocyclic groups include, but are notlimited to, azepinyl, benzodioxanyl, benzodioxolyl, benzofuranonyl,benzopyranonyl, benzopyranyl, benzotetrahydrofuranyl,benzotetrahydrothienyl, benzothiopyranyl, benzoxazinyl, β-carbolinyl,chromanyl, chromonyl, cinnolinyl, coumarinyl, decahydroisoquinolinyl,dihydrobenzisothiazinyl, dihydrobenzisoxazinyl, dihydrofuryl,dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl,dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl,1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, indolinyl,isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isochromanyl,isocoumarinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl,morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl,oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4-piperidonyl,pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl,tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydropyranyl,tetrahydrothienyl, thiamorpholinyl, thiazolidinyl, tetrahydroquinolinyl,and 1,3,5-trithianyl. In certain embodiments, heterocyclic may also beoptionally substituted as described herein.

The term “halogen”, “halide” or “halo” refers to fluorine, chlorine,bromine, and/or iodine.

The term “optionally substituted” is intended to mean that a group, suchas an alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, orheterocyclyl group, may be substituted with one or more substituentsindependently selected from, e.g., (a) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, andheterocyclyl, each optionally substituted with one or more, in oneembodiment, one, two, three, or four, substituents Q; and (b) halo,cyano (—CN), nitro (—NO₂), —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), S(O)R^(a), —S(O)₂R^(a),—S(O)NR^(b)R^(c), and —S(O)₂NR^(b)R^(c), wherein each R^(a), R^(b),R^(c), and R^(d) is independently (i) hydrogen; (ii) C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl,heteroaryl, or heterocyclyl, each optionally substituted with one ormore, in one embodiment, one, two, three, or four, substituents Q; or(iii) R^(b) and R^(c) together with the N atom to which they areattached form heteroaryl or heterocyclyl, optionally substituted withone or more, in one embodiment, one, two, three, or four, substituentsQ. As used herein, all groups that can be substituted are “optionallysubstituted,” unless otherwise specified.

In one embodiment, each Q is independently selected from the groupconsisting of (a) cyano, halo, and nitro; and (b) C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl,heteroaryl, and heterocyclyl; and (c) —C(O)R^(e), —C(O)OR^(e),—C(O)NR^(f)R^(g), —C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e),—OC(O)OR^(e), —OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e),—OS(O)₂R^(e), —OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g),—NR^(e)C(O)R^(h), —NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g),—NR^(e)C(═NR^(h))NR^(f)R^(g), —NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h),—NR^(e)S(O)NR^(f)R^(g), —NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h),—P(OR^(e))R^(h), —P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h),—P(O)(OR^(e))R^(h), —P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e),—S(O)₂R^(e), —S(O)NR^(f)R^(g), and —S(O)₂NR^(f)R^(g); wherein eachR^(e), R^(f), R^(g), and R^(h) is independently (i) hydrogen; (ii) C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅aralkyl, heteroaryl, or heterocyclyl; or (iii) R^(f) and R^(g) togetherwith the N atom to which they are attached form heteroaryl orheterocyclyl.

In certain embodiments, “optically active” and “enantiomerically active”refer to a collection of molecules, which has an enantiomeric excess ofno less than about 50%, no less than about 70%, no less than about 80%,no less than about 90%, no less than about 91%, no less than about 92%,no less than about 93%, no less than about 94%, no less than about 95%,no less than about 96%, no less than about 97%, no less than about 98%,no less than about 99%, no less than about 99.5%, or no less than about99.8%. In certain embodiments, the compound comprises about 95% or moreof one enantiomer and about 5% or less of the other enantiomer based onthe total weight of the racemate in question.

In describing an optically active compound, the prefixes R and S areused to denote the absolute configuration of the molecule about itschiral center(s). The (+) and (−) are used to denote the opticalrotation of the compound, that is, the direction in which a plane ofpolarized light is rotated by the optically active compound. The (−)prefix indicates that the compound is levorotatory, that is, thecompound rotates the plane of polarized light to the left orcounterclockwise. The (+) prefix indicates that the compound isdextrorotatory, that is, the compound rotates the plane of polarizedlight to the right or clockwise. However, the sign of optical rotation,(+) and (−), is not related to the absolute configuration of themolecule, R and S.

The term “about” or “approximately” means an acceptable error for aparticular value as determined by one of ordinary skill in the art,which depends in part on how the value is measured or determined. Incertain embodiments, the term “about” or “approximately” means within 1,2, 3, or 4 standard deviations. In certain embodiments, the term “about”or “approximately” means within 50%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%,4%, 3%, 2%, 1%, 0.5%, or 0.05% of a given value or range.

Compounds

In one embodiment, provided herein is a ruthenium complex of Formula I:

wherein:

L is a neutral ligand;

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b)—NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

X¹ and X² are each independently an anionic ligand;

Y is a bond or —NR^(b)—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OC(O)R^(e), —OC(O)R^(e), —OC(O)NR^(f)R^(g),—OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e), —OS(O)NR^(f)R^(g),—OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h), NR^(e)C(O)OR^(h),—NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(—NR^(h))NR^(f)R^(g), —NR^(e)S(O)R^(h),—NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g), —NR^(e)S(O)₂NR^(f)R^(g),—PR^(e)R^(h), —P(OR^(e))R^(h), —P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h),—P(O)(OR^(e))R^(h), —P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e),—S(O)₂R^(e), or —S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), andR^(h) is independently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or R^(f) and R^(g) together with the N atom to which they are attachedform heterocyclyl.

In another embodiment, provided herein is a ruthenium complex of FormulaI:

wherein:

L is a neutral ligand;

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

X¹ and X² are each independently an anionic ligand;

Y is a bond or —NR^(b)—;

Z is O or S;

n is an integer of 0, 1, 2, or 3;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; and

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(e), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OC(O)R^(e), —OC(O)OR^(e), —OC(O)NR^(f)R^(g),—OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e), —OS(O)NR^(f)R^(g),—OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h), —NR^(e)C(O)OR^(h),—NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g), —NR^(e)S(O)R^(h),—NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g), —NR^(e)S(O)₂NR^(f)R^(g),—PR^(e)R^(h), —P(OR^(e))R^(h), —P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h),—P(O)(OR^(e))R^(h), —P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e),—S(O)₂R^(e), or —S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), andR^(h) is independently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or R^(f) and R^(g) together with the N atom to which they are attachedform heterocyclyl.

In one embodiment, provided herein is a ruthenium complex of Formula Ia:

wherein:

L is a neutral ligand;

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl; X¹ and X² are each independently ananionic ligand;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —S(O)R^(e), —S(O)₂R^(e), or —S(O)₂NR^(f)R^(g);wherein each R^(e), R^(f), R^(g), and R^(h) is independently hydrogen;C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; or R^(f) and R^(g) togetherwith the N atom to which they are attached form heterocyclyl.

In another embodiment, provided herein is a ruthenium complex of FormulaIa:

wherein:

L is a neutral ligand;

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

X¹ and X² are each independently an anionic ligand;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —P(OR^(e))R^(h), —P(OR^(e))(OR^(h)),—P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h), —P(O)(OR^(e))(OR^(h)), —SR^(e),—S(O)R^(e), —S(O)₂R^(e), or —S(O)₂NR^(f)R^(g); wherein each R^(e),R^(f), R^(g), and R^(h) is independently hydrogen; C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl,heteroaryl, or heterocyclyl; or R^(f) and R^(g) together with the N atomto which they are attached form heterocyclyl.

In yet another embodiment, provided herein is a ruthenium complex ofFormula Ib:

wherein:

L is a neutral ligand;

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

X¹ and X² are each independently an anionic ligand;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(PR^(a)R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In yet another embodiment, provided herein is a ruthenium complex ofFormula Ib:

wherein:

L is a neutral ligand;

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

X¹ and X² are each independently an anionic ligand;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(b))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —P(OR^(e))R^(h), —P(OR^(e))(OR^(h)),—P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h), —P(O)(OR^(e))(OR^(h)), —SR^(e),—S(O)R^(e), —S(O)₂R^(e), or —S(O)₂NR^(f)R^(g); wherein each R^(e),R^(f), R^(g), and R^(h) is independently hydrogen; C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl,heteroaryl, or heterocyclyl; or R^(f) and R^(g) together with the N atomto which they are attached form heterocyclyl.

In yet another embodiment, the compound is a ruthenium complex ofFormula Ic:

wherein:

L is a neutral ligand;

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

X¹ and X² are each independently an anionic ligand;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In yet another embodiment, the compound is a ruthenium complex ofFormula Ic:

wherein:

L is a neutral ligand;

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

X¹ and X² are each independently an anionic ligand;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆, alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In yet another embodiment, provided herein is a compound of Formula II:

wherein:

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

Y is a bond or —NR^(b)—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In still another embodiment, provided herein is a compound of FormulaII:

wherein:

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b)—NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

Y is a bond or —NR^(b)—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(c)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In one embodiment, provided herein is a compound of Formula IIa:

wherein:

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(—NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(h); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In another embodiment, provided herein is a compound of Formula IIa:

wherein:

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a) and R^(ad) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In yet another embodiment, provided herein is a compound of Formula IIb:

wherein:

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl; R^(4a) and R^(4b) are each independentlyhydrogen, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In yet another embodiment, provided herein is a compound of Formula IIb:

wherein:

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3d))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In yet another embodiment, provided herein is a compound of Formula IIc:

wherein:

R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d);

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl;

R^(4c) and R^(4d) are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) togetherwith the N atom form heterocyclyl;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, aryl, C₇₋₁₅aralkyl, heteroaryl, or heterocyclyl, each optionally substituted withone or more, in one embodiment, one, two, three, or four, substituentsQ; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

In yet another embodiment, provided herein is a compound of Formula IIc;

wherein:

R¹ is C₁₋₁₂ alkyl, CO₃₋₁₀ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c);

R² is H, C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl;

R³ is halo, cyano, nitro, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl, —C(O)R^(3a),—C(O)OR^(3a), —C(O)NR^(3b)R^(3c), —OR^(3a), —NR^(3b)R^(3c),—NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b), —NR^(3a)S(O)₂R^(3b),—PR^(3a)R^(3b), —P(OR^(3a))R^(3b), —P(OR^(3a))(OR^(3b)),—P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b), —P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c),

R⁴ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl, or C₇₋₁₅ aralkyl;

R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂ alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀cycloalkyl, or C₆₋₁₄ aryl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a) and R^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl;

each R^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, orheterocyclyl; or R^(3b) and R^(3c) together with the N atom form aheteroaryl or heterocyclyl;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₄ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more, in one embodiment, one, two, three, or four,substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a), —C(O)NR^(b)R^(c),—C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a), —OC(O)OR^(a),—OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a), —OS(O)₂R^(a),—OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c), —NR^(a)C(O)R^(d),—NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c), —NR^(a)C(═NR^(d))NR^(b)R^(c),—NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d), —NR^(a)S(O)NR^(b)R^(c),—NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d), —P(OR^(a))R^(d),—P(OR_(a))(OR^(d)), —P(O)R^(a)R^(d), —P(O)(OR^(a))R^(d),—P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a), —S(O)₂R^(a), or—SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), and R^(d) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, eachoptionally substituted with one or more, in one embodiment, one, two,three, or four, substituents Q; or R^(b) and R^(c) together with the Natom to which they are attached form heterocyclyl, optionallysubstituted with one or more, in one embodiment, one, two, three, orfour, substituents Q;

wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.

The groups in Formulae I, Ia, Ib, Ic, II, IIa, IIb, and IIc, includingR¹, R², R³, R⁴, R⁵, R⁶, R⁷, R^(4a), R^(4b), R^(4c), R^(4d), L, X¹, X²,Z, Y, and n, are further defined in the following embodiments,independently or in combination. All combinations of such embodimentsare within the scope of this disclosure.

In certain embodiments, R¹ is C₁₋₁₂ alkyl, optionally substituted withone or more substituents as described herein. In certain embodiments, R¹is C₁₋₅ alkyl, optionally substituted with one or more substituents asdescribed herein. In certain embodiments, R¹ is C₁₋₅ alkyl, optionallysubstituted with one or more halo. In certain embodiments, R¹ istrifluoromethyl. In certain embodiments, R¹ is C₃₋₁₀ cycloalkyl,optionally substituted with one or more substituents as describedherein. In certain embodiments, R¹ is C₅₋₆ cycloalkyl, optionallysubstituted with one or more substituents as described herein.

In certain embodiments, R¹ is C₆₋₁₄ aryl, optionally substituted withone or more substituents as described herein. In certain embodiments, R¹is C₆₋₁₄ aryl, substituted with one or more substituents, eachindependently selected from the group consisting of cyano, halo, nitro,trifluoromethyl, methoxy, trifluoromethylsulfonyl, trifluoroacetyl, andtrifluoroacetamido. In certain embodiments, R¹ is phenyl. In certainembodiments, R¹ is phenyl, substituted with one or more substituents asdescribed herein. In certain embodiments, R¹ is phenyl, substituted withone or more substituents, each independently selected from the groupconsisting of cyano, halo, nitro, trifluoromethyl, methoxy,trifluoromethyl-sulfonyl, trifluoroacetyl, and trifluoroacetamido. Incertain embodiments, R¹ is phenyl, cyanophenyl (e.g., 2-, 3-, or4-cyanophenyl), fluorophenyl (e.g., 2-, 3-, or 4-fluorophenyl),difluorophenyl (e.g., 2,4- or 3,5-difluorophenyl), trifluoromethylphenyl(e.g., 2-, 3-, or 4-trifluoromethylphenyl), bis(trifluoromethyl)phenyl(e.g., 3,5-bis(trifluoromethyl)-phenyl), methoxy-phenyl (e.g., 2-, 3-,or 4-methoxyphenyl), trifluoromethylsulfonylphenyl (e.g., 2-, 3-, or4-trifluoromethylsulfonylphenyl), trifluoroacetylphenyl (e.g., 2-, 3-,or 4-trifluoroacetylphenyl), nitrophenyl (e.g., 2-, 3-, or4-nitrophenyl), dinitrophenyl (e.g., 3,5-dinitrophenyl),trifluoroacetamidophenyl (e.g., 2-, 3-, 4-trifluoroacetamidophenyl), orpentofluorophenyl. In certain embodiments, R¹ is phenyl, 4-cyanophenyl,4-fluorophenyl, 3,5-difluorophenyl, 4-trifluoromethylphenyl,3,5-bis(trifluoromethyl)phenyl, 4-methoxy-phenyl,4-trifluoromethylsulfonylphenyl, 4-trifluoroacetylphenyl, 4-nitrophenyl,3,5-dinitrophenyl, 4-trifluoroacetamidophenyl, or pentofluorophenyl.

In certain embodiments, R¹ is heteroaryl, optionally substituted withone or more substituents as described herein. In certain embodiments, R¹is pyridyl, thiazolyl, or pyrazolyl, each optionally substituted withone or more substituents as described herein. In certain embodiments, R¹is pyridyl, thiazolyl, or pyrazolyl, each optionally substituted withone or more substituents, each independently selected from the groupconsisting of cyano, halo, nitro, trifluoromethyl, methoxy,trifluoromethyl-sulfonyl, trifluoroacetyl, and trifluoroacetamido. Incertain embodiments, R¹ is pyridyl, trifluoromethyl-thiazolyl (e.g., 2-,4-, or 5-trifluoro-methylthiazolyl), or trifluoromethyl-pyrazolyl (e.g.,3- or 4-trifluoromethylpyrazolyl). In certain embodiments, R¹ ispyridyl, 4-trifluoromethylthiazolyl, or 3-trifluoromethyl-pyrazolyl.

In certain embodiments R¹ is —NR^(3b)R^(3c); wherein R^(3b) and R^(3c)are each as defined herein. In certain embodiments, R^(3b) is hydrogenor C₁₋₆ alkyl, optionally substituted with one or more substituents asdescribed herein. In certain embodiments, R^(3b) is hydrogen, methyl,ethyl, or propyl. In certain embodiments, R^(3c) is hydrogen or C₁₋₆alkyl, optionally substituted with one or more substituents as describedherein. In certain embodiments, R^(3c) is hydrogen, methyl, ethyl, orpropyl. In certain embodiments R¹ is C₁₋₆ alkylamino, optionallysubstituted with one or more substituents as described herein. Incertain embodiments R¹ is di(C₁₋₆ alkylamino, each alkyl optionallysubstituted with one or more substituents as described herein. Incertain embodiments R¹ is dimethylamino.

In certain embodiments, R² is C₁₋₅ alkyl, optionally substituted withone or more substituents as described herein. In certain embodiments, R²is ethyl. In certain embodiments, R² is C₅₋₆ cycloalkyl, optionallysubstituted with one or more substituents as described herein.

In certain embodiments, R³ is halo. In certain embodiments, R³ is chloroor fluoro. In certain embodiments, R³ is nitro. In certain embodiments,R³ is C₁₋₁₂ alkyl, optionally substituted with one or more substituentsas described herein. In certain embodiments, R³ is C₃₋₁₀ cycloalkyl,optionally substituted with one or more substituents as describedherein. In certain embodiments, R³ is C₆₋₁₄ aryl, optionally substitutedwith one or more substituents as described herein. In certainembodiments, R³ is —OR^(3a), wherein R^(3a) is as defined herein. Incertain embodiments, R³ is —SO₂NR^(3a)R^(3b), wherein R^(3a) and R^(3b)are each as defined herein. In certain embodiments, R³ is—P(O)(OR²)(R¹), wherein R¹ and R² are each as defined herein. In certainembodiments, R³ is —CO₂R^(3a), wherein R^(3a) is as defined herein. Incertain embodiments, R³ is —NR^(3a)SO₂R^(3b), wherein R^(3a) and R^(3b)are each as defined herein. In certain embodiments, each R^(3a) isindependently C₁₋₁₂ alkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, each R^(3a) isC₃₋₁₀ cycloalkyl, optionally substituted with one or more substituentsas described herein. In certain embodiments, each R^(3b) isindependently C₁₋₁₂ alkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, each R^(3b) isC₃₋₁₀ cycloalkyl, optionally substituted with one or more substituentsas described herein.

In certain embodiments, R⁴ is C₁₋₅ alkyl, optionally substituted withone or more substituents as described herein. In certain embodiments, R⁴is C₅₋₆ cycloalkyl, optionally substituted with one or more substituentsas described herein. In certain embodiments, R⁴ is propyl (e.g.,n-propyl or isopropyl). In certain embodiments, R⁴ is isopropyl. Incertain embodiments, R⁴ is C₇₋₁₅ aralkyl, optionally substituted withone or more substituents as described herein. In certain embodiments, R⁴is —C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d), wherein R^(4a), R^(4b), R^(4c),and R^(4d) are each as defined herein.

In certain embodiments, R⁵ is hydrogen. In certain embodiments, R⁵ isC₁₋₅ alkyl, optionally substituted with one or more substituents asdescribed herein. In certain embodiments, R⁵ is C₅₋₆ cycloalkyl,optionally substituted with one or more substituents as describedherein.

In certain embodiments, R⁶ is hydrogen. In certain embodiments, R⁷ ishydrogen. In certain embodiments, R⁶ and R⁷ are hydrogen.

In certain embodiments, R^(4a) is hydrogen. In certain embodiments,R^(4a) is C₁₋₆ alkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, R^(4a) is C₃₋₈cycloalkyl, optionally substituted with one or more substituents asdescribed herein. In certain embodiments, R^(4a) is C₆₋₁₄ aryl,optionally substituted with one or more substituents as describedherein. In certain embodiments, R^(4a) is C₇₋₁₅ aralkyl, optionallysubstituted with one or more substituents as described herein.

In certain embodiments, R^(4b) is hydrogen. In certain embodiments,R^(4b) is C₁₋₆ alkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, R^(4b) is C₃₋₈cycloalkyl, optionally substituted with one or more substituents asdescribed herein. In certain embodiments, R^(4b) is C₆₋₁₄ aryl,optionally substituted with one or more substituents as describedherein. In certain embodiments, R^(4b) is C₇₋₁₅ aralkyl, optionallysubstituted with one or more substituents as described herein.

In certain embodiments, R^(4c) is hydrogen. In certain embodiments,R^(4c) is C₁₋₆ alkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, R^(4c) is C₃₋₈cycloalkyl, optionally substituted with one or more substituents asdescribed herein. In certain embodiments, R^(4c) is C₆₋₁₄ aryl,optionally substituted with one or more substituents as describedherein. In certain embodiments, R^(4c) is C₇₋₁₅ aralkyl, optionallysubstituted with one or more substituents as described herein.

In certain embodiments, R^(4d) is hydrogen. In certain embodiments,R^(4d) is C₁₋₆ alkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, R^(4d) is C₃₋₈cycloalkyl, optionally substituted with one or more substituents asdescribed herein. In certain embodiments, R^(4d) is C₆₋₁₄ aryl,optionally substituted with one or more substituents as describedherein. In certain embodiments, R^(4d) is C₇₋₁₅ aralkyl, optionallysubstituted with one or more substituents as described herein.

In certain embodiments, R^(4c) and R^(4d) together with the N atom formheterocyclyl, optionally substituted with one or more substituents asdescribed herein. In certain embodiments, R^(4c) and R^(4d) togetherwith the N atom form 5- to 8-membered heterocyclyl, optionallysubstituted with one or more substituents as described herein. Incertain embodiments, R^(4c) and R^(4d) together with the N atom form 5-to 8-membered heterocyclyl, which may contains one or more heteroatoms,each independently selected from nitrogen, oxygen, and sulfur, whereinthe heterocyclyl is optionally substituted with one or more substituentsas described herein.

In certain embodiments, L is a heterocyclic carbene, optionallysubstituted with one or more substituents as described herein. Incertain embodiments, L is selected from the group consisting of:

wherein:

each R¹¹ and R¹² is independently C₁₋₆ alkyl or C₆₋₁₄ aryl; and

each R¹³, R¹⁴, R¹⁵, and R¹⁶ is independently hydrogen, cyano, nitro,C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,heteroaryl, or heterocyclyl;

wherein each alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl,and heteroaryl is optionally substituted with one or more substituents.

In certain embodiments, R¹¹ is C₁₋₆ alkyl, optionally substituted withone or more substituents. In certain embodiments, R¹¹ is C₁₋₆ aryl,optionally substituted with one or more substituents. In certainembodiments, R¹¹ is C₆₋₁₄ aryl, substituted with one or more C₁₋₆ alkyl.In certain embodiments, R¹¹ is methylphenyl, trimethylphenyl, ordi(isopropyl)phenyl. In certain embodiments, R¹¹ is 2-methylphenyl,2,4,6-trimethylphenyl, or 2,6-di(isopropyl)phenyl.

In certain embodiments, R¹² is C₁₋₆ alkyl, optionally substituted withone or more substituents. In certain embodiments, R¹² is C₁₋₆ aryl,optionally substituted with one or more substituents. In certainembodiments, R¹² is C₆₋₁₄ aryl, substituted with one or more C₁₋₆ alkyl.In certain embodiments, R¹² is methylphenyl, trimethylphenyl, ordi(isopropyl)phenyl. In certain embodiments, R¹² is 2-methylphenyl,2,4,6-trimethylphenyl, or 2,6-di(isopropyl)phenyl.

In certain embodiments, R¹¹ and R¹² are trimethylphenyl. In certainembodiments, R¹¹ and R¹² are 2,4,6-trimethylphenyl. In certainembodiments, R¹¹ and R¹² are di(isopropyl)phenyl. In certainembodiments, R¹¹ and R¹² are 2,6-di(isopropyl)phenyl. In certainembodiments, R¹¹ and R¹² are methylphenyl. In certain embodiments, R¹¹and R¹² are 2-methylphenyl.

In certain embodiments, R¹³ is hydrogen. In certain embodiments, R¹³ isC₁₋₆ alkyl, optionally substituted with one or more substituents. Incertain embodiments, R¹³ is methyl.

In certain embodiments, R¹⁴ is hydrogen. In certain embodiments, R¹⁴ isC₁₋₆ alkyl, optionally substituted with one or more substituents. Incertain embodiments, R¹⁴ is methyl.

In certain embodiments, R¹⁵ is hydrogen. In certain embodiments, R¹⁵ isC₁₋₆ alkyl, optionally substituted with one or more substituents. Incertain embodiments, R¹⁵ is methyl.

In certain embodiments, R¹⁶ is hydrogen. In certain embodiments, R¹⁶ isC₁₋₆ alkyl, optionally substituted with one or more substituents. Incertain embodiments. R¹⁶ is methyl.

In certain embodiments, R¹³, R¹⁴, R¹⁵, and R¹⁶ are hydrogen. In certainembodiments, R¹³, R¹⁴, R¹⁵, and R¹⁶ are methyl.

In certain embodiments, L is one selected from:

In certain embodiments, L is a phosphine. In certain embodiments, L is aP of PR¹⁷R¹⁸R¹⁹, where R¹⁷, R¹⁸, and R¹⁹ are each independently C₁₋₁₂alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl, each optionally substituted withone or more substituents as described herein.

In certain embodiments, R¹⁷ is C₁₋₁₂ alkyl, optionally substituted withone or more substituents as described herein. In certain embodiments,R¹⁷ is C₃₋₁₀ cycloalkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, R¹⁷ iscyclohexyl. In certain embodiments, R¹⁷ is C₆₋₁₄ aryl, optionallysubstituted with one or more substituents as described herein. Incertain embodiments, R¹⁷ is phenyl.

In certain embodiments, R¹⁸ is C₁₋₁₂ alkyl, optionally substituted withone or more substituents as described herein. In certain embodiments,R¹⁸ is C₃₋₁₀ cycloalkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, R¹⁸ iscyclohexyl. In certain embodiments, R¹⁸ is C₆₋₁₄ aryl, optionallysubstituted with one or more substituents as described herein. Incertain embodiments, R¹⁸ is phenyl.

In certain embodiments, R¹⁹ is C₁₋₁₂ alkyl, optionally substituted withone or more substituents as described herein. In certain embodiments,R¹⁹ is C₃₋₁₀ cycloalkyl, optionally substituted with one or moresubstituents as described herein. In certain embodiments, R¹⁹ iscyclohexyl. In certain embodiments, R¹⁹ is C₆₋₁₄ aryl, optionallysubstituted with one or more substituents as described herein. Incertain embodiments, R¹⁹ is phenyl.

In certain embodiments, L is triphenylphosphine ortricyclohexylphosphine.

In certain embodiments, X¹ is halide. In certain embodiments, X¹ isfluoride, chloride, bromide, or iodide. In certain embodiments, X¹ ischloride. In certain embodiments, X¹ is —C(O)R^(x) or —OC(O)R^(x) whereR^(x) is C₁₋₆ alkyl, optionally substituted with one or more halides.

In certain embodiments, X² is halide. In certain embodiments, X² isfluoride, chloride, bromide, or iodide. In certain embodiments, X² ischloride. In certain embodiments, X² is —C(O)R^(x) or —OC(O)R^(x) whereR^(x) is C₁₋₆ alkyl, optionally substituted with one or more halides.

In certain embodiments, Y is a bond. In certain embodiments, Y is—NR^(b)—, wherein R^(b) is as defined herein. In certain embodiments, Yis —NH—.

In certain embodiments, Z is O. In certain embodiments, Z is S.

In certain embodiments, n is 0. In certain embodiments, n is 1. Incertain embodiments, n is 2. In certain embodiments, n is 3.

In one embodiment, provided herein is the ruthenium complex of FormulaI, wherein:

L is a heterocyclic carbene or phosphine;

R¹ is C₁₋₅ alkyl, C₅₋₆ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl,or —NR^(3b)R^(3c);

R² is C₁₋₅ alkyl or C₅₋₆ cycloalkyl;

R³ is halo, cyano, nitro, —C(O)OR^(3a), —NR^(3a)S(O)₂R^(3b),—P(O)(OR^(3a))R^(3b), or —SO₂NR^(3b)R^(3c);

R⁴ is C₁₋₅ alkyl or C₅₋₆ cycloalkyl;

R⁵ is hydrogen, C₁₋₅ alkyl, or C₅₋₆ cycloalkyl;

each R^(3a), R^(3b), and R^(3c) is as defined herein;

X¹ and X² are each independently an anionic ligand;

Y is a bond or —NR^(b)—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, aryl, cycloalkyl, heterocyclyl, heterocycliccarbene, and heteroaryl is optionally substituted with one or moresubstituents as described herein.

In another embodiment, provided herein is the ruthenium complex ofFormula I, wherein:

L is triphenylphosphine, tricyclohexylphosphine, or a heterocycliccarbene selected from:

R¹ is C₁₋₅ alkyl, C₅₋₆ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl,or —NR^(3b)R^(3c);

R² is C₁₋₅ alkyl or C₅₋₆ cycloalkyl;

R³ is halo, cyano, nitro, —C(O)OR^(3a), —NR^(3a)S(O)₂R^(3b),—P(O)(OR^(3a))R^(3b), or —SO₂NR^(3b)R³;

R⁴ is C₁₋₅ alkyl or C₅₋₆ cycloalkyl;

R⁵ is hydrogen, C₁₋₅ alkyl, or C₅₋₆ cycloalkyl;

each R^(3a), R^(3b), and R^(3c) is as defined herein;

X¹ and X² are each independently an anionic ligand;

Y is a bond or —NR^(b)—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, aryl, cycloalkyl, heterocyclyl, and heteroaryl isoptionally substituted with one or more substituents as describedherein.

In yet another embodiment, provided herein is the ruthenium complex ofFormula I, wherein:

L is triphenylphosphine, tricyclohexylphosphine, or a heterocycliccarbene selected from:

R¹ is trifluoromethyl, phenyl, cyanophenyl, fluorophenyl,difluorophenyl, trifluoromethylphenyl, bis(trifluoromethyl)phenyl,methoxyphenyl, trifluoromethylsulfonylphenyl, trifluoroacetylphenyl,nitrophenyl, dinitrophenyl, trifluoroacetamidophenyl, pentofluorophenyl,pyridyl, trifluoromethyl-thiazolyl, trifluoromethyl-pyrazolyl, ordimethylamino;

R² is ethyl;

R⁴ is isopropyl;

R⁵ is hydrogen;

Y is a bond or —NH—;

X¹ and X² are chloride;

Z is O; and

n is 0.

In yet another embodiment, provided herein is the ruthenium complex ofFormula I, wherein:

L is triphenylphosphine, tricyclohexylphosphine, or a heterocycliccarbene selected from:

R¹ is phenyl, 4-cyanophenyl, 4-fluorophenyl, 3,5-difluorophenyl,4-trifluoromethylphenyl), 3,5-bis(trifluoromethyl)phenyl,4-methoxyphenyl, 4-trifluoromethylsulfonylphenyl,4-trifluoroacetylphenyl, 4-nitrophenyl, 3,5-dinitrophenyl,4-trifluoroacetamidophenyl, pentotluorophenyl, pyridyl,4-trifluoromethylthiazolyl, 3-trifluoromethyl-pyrazolyl, ordimethylamino;

R² is ethyl;

R⁴ is isopropyl;

R⁵ is hydrogen;

X¹ and X² are chloride;

Y is a bond or —NH—;

Z is O; and

n is 0.

In still another embodiment, provided herein is a ruthenium complexselected from:

wherein:

Cmpd No. Y R¹ R¹¹ R¹² AP A bond

Mes Mes AQ A bond

Mes Mes AR A bond

Mes Mes AT A bond

Mes Mes C5 A bond —N(CH₃)₂ Mes Mes D4 A bond

Mes Mes E6 —NH—

Mes Mes G2 A bond

2-MePh 2-MePh Mes: 2,4,6-trimethylphenyl 2-MePh: 2-methylphenyl

In one embodiment, provided herein is the compound of Formula II,wherein:

R¹ is C₁₋₅ alkyl, C₅₋₆ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl,or —NR^(3b)R^(3c);

R² is C₁₋₅ alkyl or C₅₋₆ cycloalkyl;

R³ is halo, cyano, nitro, —C(O)OR^(3a), —NR^(3a)S(O)₂R^(3b),—P(O)(OR^(3a))R^(3b), or —SO₂NR^(3b)R^(3c);

R⁴ is C₁₋₅ alkyl or C₅₋₆ cycloalkyl;

R⁵ is hydrogen, C₁₋₅ alkyl, or C₅₋₆ cycloalkyl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a), R^(3b), and R^(3c) is as defined herein;

Y is a bond or —NH—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, aryl, cycloalkyl, heterocyclyl, heterocycliccarbene, and heteroaryl is optionally substituted with one or moresubstituents as described herein.

In another embodiment, provided herein is the compound of Formula II,wherein:

R¹ is C₁₋₅ alkyl, C₅₋₆ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, heterocyclyl,or —NR^(3b)R^(3c);

R² is C₁₋₅ alkyl or C₅₋₆ cycloalkyl;

R³ is halo, cyano, nitro, —C(O)OR^(3a), —NR^(3a)S(O)₂R^(3b),—P(O)(OR^(3a))R^(3b), or —SO₂NR^(3b)R^(3c); R⁴ is C₁₋₅ alkyl or C₅₋₆cycloalkyl;

R⁵ is hydrogen, C₁₋₅ alkyl, or C₅₋₆ cycloalkyl;

R⁶ and R⁷ are independently hydrogen or C₁₋₆ alkyl;

each R^(3a), R^(3b), and R^(3c) is as defined herein;

Y is a bond or —NH—;

Z is O or S; and

n is an integer of 0, 1, 2, or 3;

wherein each alkyl, aryl, cycloalkyl, heterocyclyl, and heteroaryl isoptionally substituted with one or more substituents as describedherein.

In yet another embodiment, provided herein is the compound of FormulaII, wherein:

R¹ is trifluoromethyl, phenyl, cyanophenyl, fluorophenyl,difluorophenyl, trifluoromethylphenyl, bis(trifluoromethyl)phenyl,methoxyphenyl, trifluoromethylsulfonylphenyl, trifluoroacetylphenyl,nitrophenyl, dinitrophenyl, trifluoroacetamidophenyl, pentofluorophenyl,pyridyl, trifluoromethyl-thiazolyl, trifluoromethyl-pyrazolyl, ordimethylamino;

R² is ethyl;

R⁴ is isopropyl;

R⁵ is hydrogen;

R⁶ and R⁷ are hydrogen;

Y is a bond or —NH—;

Z is O; and

n is 0.

In yet another embodiment, provided herein is the compound of FormulaII, wherein:

R¹ is phenyl, 4-cyanophenyl, 4-fluorophenyl, 3,5-difluorophenyl,4-trifluoromethylphenyl), 3,5-bis(trifluoromethyl)phenyl,4-methoxyphenyl, 4-trifluoromethylsulfonylphenyl,4-trifluoroacetylphenyl, 4-nitrophenyl, 3,5-dinitrophenyl,4-trifluoroacetamidophenyl, pentotluorophenyl, pyridyl,4-trifluoromethylthiazolyl, 3-trifluoromethyl-pyrazolyl, ordimethylamino;

R² is ethyl;

R⁴ is isopropyl;

R⁵ is hydrogen;

R⁶ and R⁷ are hydrogen;

Y is a bond or —NH—;

Z is O; and

n is 0.

In still another embodiment, provided herein is a compound selectedfrom:

wherein:

Cmpd No. Y R¹ BA1 A bond

BA4 A bond

BA2 A bond

BA3 A bond

C4 A bond —N(CH₃)₂ D3 A bond

E5 —NH—

The compounds provided herein are intended to encompass all possiblestereoisomers, unless a particular stereochemistry is specified. Wherethe compound provided herein contains an alkenyl or alkenylene group,the compound may exist as one or a mixture of geometric cis/trans (orZ/E) isomers. Where structural isomers are interconvertible, thecompound may exist as a single tautomer or a mixture of tautomers. Thiscan take the form of proton tautomerism in the compound that contains,for example, an imino, keto, or oxime group; or so-called valencetautomerism in the compound that contain an aromatic moiety. It followsthat a single compound may exhibit more than one type of isomerism.

In certain embodiments, the compound of Formula I, where R⁴ is—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d), also encompasses the structure of:

The compounds provided herein may be enantiomerically pure, such as asingle enantiomer or a single diastereomer, or be stereoisomericmixtures, such as a mixture of enantiomers, e.g., a racemic mixture oftwo enantiomers; or a mixture of two or more diastereomers. As such, oneof skill in the art will recognize that administration of a compound inits (R) form is equivalent, for compounds that undergo epimerization invivo, to administration of the compound in its (S) form. Conventionaltechniques for the preparation/isolation of individual enantiomersinclude synthesis from a suitable optically pure precursor, asymmetricsynthesis from achiral starting materials, or resolution of anenantiomeric mixture, for example, chiral chromatography,recrystallization, resolution, diastereomeric salt formation, orderivatization into diastereomeric adducts followed by separation.

Methods of Synthesis

The compound provided herein can be prepared, isolated, or obtained byany method known to one of skill in the art. For an example, compoundsof Formulae I to IV can be prepared as shown in Scheme 1.

Olefin Metathesis

In one embodiment, provided herein is a method for catalyzing an olefinmetathesis reaction, which comprises the step of contacting an olefincompound with a ruthenium complex of Formula I. Tn certain embodiments,the olefin compound has one terminal olefin group. In certainembodiments, the molar ratio between the ruthenium complex of Formula Iand the olefin compound is no greater than about 0.5, no greater thanabout 0.4, no greater than about 0.3, no greater than about 0.2, nogreater than about 0.1, no greater than about 0.08, no greater thanabout 0.06, no greater than about 0.05, no greater than about 0.04, nogreater than about 0.03, no greater than about 0.02, or no greater thanabout 0.01.

In another embodiment, provided herein is a method for catalyzing a ringclosure metathesis, which comprises the step of contacting an olefincompound having two or more olefin groups with a ruthenium complex ofFormula I. In certain embodiments, the olefin compound has one terminalolefin group. In certain embodiments, the olefin compound has twoterminal olefin groups. In certain embodiments, the molar ratio betweenthe ruthenium complex of Formula I and the olefin compound is no greaterthan about 0.5, no greater than about 0.4, no greater than about 0.3, nogreater than about 0.2, no greater than about 0.1, no greater than about0.08, no greater than about 0.06, no greater than about 0.05, no greaterthan about 0.04, no greater than about 0.03, no greater than about 0.02,or no greater than about 0.01.

The ruthenium complex of Formula I as an olefin metathesis catalystprovides several advantages over the existing metathesis catalysts. Incertain embodiments, the ruthenium complex of Formula I provides bettercatalytic efficiency for either olefin metathesis or ring closuremetathesis reaction. In certain embodiments, the ruthenium complex ofFormula I provides better yield for either olefin metathesis or ringclosure metathesis reaction. In certain embodiments, the rutheniumcomplex of Formula I provides better chiral purity of the desiredproduct produced via either olefin metathesis or ring closure metathesisreaction. In certain embodiments, the ruthenium complex of Formula Iprovides less metal contamination in the desired product produced viaeither olefin metathesis or ring closure metathesis reaction.

The disclosure will be further understood by the following non-limitingexamples.

EXAMPLES

As used herein, the symbols and conventions used in these processes,schemes and examples, regardless of whether a particular abbreviation isspecifically defined, are consistent with those used in the contemporaryscientific literature, for example, the Journal of the American ChemicalSociety or the Journal of Biological Chemistry. Specifically, butwithout limitation, the following abbreviations may be used in theexamples and throughout the specification: g (grams); mg (milligrams);mL (milliliters); μL (microliters); mM (millimolar); μM (micromolar); Hz(Hertz); MHz (megahertz); mmol (millimoles); eq. (equivalent); hr or hrs(hours); min (minutes); MS (mass spectrometry); NMR (nuclear magneticresonance); ESI (electrospray ionization); ACN, (acetonitrile); CDCl₃(deuterated chloroform); DCE (dichloroethane); DCM (dichloromethane);DMF (N,N-dimethylformamide); DMSO (dimethylsulfoxide); DMSO-d₆(deuterated dimethylsulfoxide); EtOAc (ethyl acetate); MeOH (methanol);THF (tetrahydrofuran); DIPEA (N,N-diisopropylethylamine); TEA(triethylamine); DBU (1,8-diazabicyclo[5.4.0]undec-7-ene; CDI(carbonyldiimidazole); EDCI or EDC(N′-ethyl-N-(3-dimethylaminopropyl)-carbodiimide); P₂O₅, (phosphoruspentoxide); TBAF (tetrabutylammonium fluoride); TBTU(O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate);Me (methyl); Et (ethyl); iPr, (isopropyl); tBu (tert-butyl); Boc(tert-butoxylcarbony); Bn (benzyl); PMB (p-methoxybenzyl); TsO(tosylate); DEAD (diethylazodicarboxylate), DIAD(diisopropylazodicarboxylate), PPh₃ (triphenylphosphine), PNBA(p-nitrobenzoic acid), PNB (p-nitrobenzoyl), and Mes (mesityl or2,4,6-trimethylphenyl).

For all of the following examples, standard work-up and purificationmethods known to those skilled in the art can be utilized. Unlessotherwise indicated, all temperatures are expressed in ° C. (degreesCentigrade). All reactions conducted at room temperature unlessotherwise noted. Synthetic methodologies illustrated in the schemesshown herein are intended to exemplify the applicable chemistry throughthe use of specific examples and are not indicative of the scope of thedisclosure.

Example 1 Synthesis of Ruthenium Complexes

Ruthenium complexes, such as AP, AQ, AR, and AT, were prepared as shownin Scheme 2.

Step A: Preparation of 5-bromo-2-isopropoxybenzaldehyde AX. To asuspension of potassium carbonate (34.4 g, 249 mmol) and cesiumcarbonate (16.2 g, 50 mmol) in dimethylformamide were added5-bromosalicaldehyde (25.0 g, 124 mmol) and 2-iodopropane (25.0 mL, 249mmol). The suspension was stirred at room temperature overnight, then at70° C. for 4 hrs. The volatiles were removed, and the residue waspartitioned between methyl t-butylether and water. The aqueous layer wasextracted with methyl t-butylether and the combined organic phases werewashed with water, sodium hydroxide, and brine, and then dried overmagnesium sulfate. Concentration to dryness afforded compound AX (30.0g) as a pale yellow oil in 99% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm)1.40 (d, J=6.3 Hz, 6H), 4.65 (sept., J=6.0 Hz, 1H), 6.89 (d, J=9.0 Hz,1H), 7.59 (dd, J=9.0 and 2.7 Hz, 1H), 7.91 (d, J=2.7 Hz, 1H), 10.39 (s,1H).

Step B: Preparation of 4-bromo-1-isopropoxy-2-vinylbenzene AY. To asuspension of methyltriphenylphosphonium bromide (41.1 g, 115 mmol) inanhydrous THF (1.2 L) was added n-butyllithium (123 mmol, 2.5 M inhexanes) at −70° C. The mixture was stirred for a further 10 min, andthen allowed to warm up to 0° C. and stirred at this temperature for 10min. The reaction mixture is then cooled again at −50° C., and5-bromo-2-isopropoxybenzaldehyde (20.0 g, 82.2 mmol) in solution inanhydrous THF (5 mL) was added. The mixture was stirred for 10 min, andthen allowed to warm up to room temperature. An ammonium chloridesolution was added and the reaction mixture was diluted with a mixturemethyl t-butylether/hexane, filtered through celite, and then dried overmagnesium sulfate. The solvent was removed in vacuo to afford compoundAY (18.9 g) as a pale yellow oil in 95% yield. ¹H NMR (CDCl₃, 400 MHz):δ (ppm) 1.34 (d, J=6.0 Hz, 6H), 4.50 (sept., J=6.0 Hz, 1H), 5.27 (dd,J=11.0 and 1.1 Hz, 1H), 5.71 (dd, J=17.9 and 1.2 Hz, 1H), 6.75 (d, J=8.7Hz, 1H), 6.97 (dd, J=17.7 and 11.2 Hz, 1H), 7.28 (dd, J=8.7 and 2.5 Hz,1H), 7.57 (d, J=2.5 Hz, 1H).

Preparation of Ruthenium Complex AP

Step A: Preparation of ethyl 4-(trifluoromethyl)phenylphosphinate AZ1.To a degassed solution of 4-iodobenzotrifluoride (4.70 g, 17.2 mmol),anilinium hypophosphite (3.51 g, 22.1 mmol), and 3-aminopropyltriethoxysilane (4.88 g, 22.1 mmol) in anhydrous acetonitrile (110 mL)were added palladium acetate (82.5 mg, 0.367 mmol, 2 mol %) and1,3-bis(diphenylphosphino)propane (167 mg, 0.404 mol, 2.2 mol %). Themixture was refluxed for 32 hrs. After cooling down to room temperature,the reaction mixture was diluted with ethyl acetate and hydrochloricacid (1M), and partitioned. The aqueous layer was further extracted withethyl acetate. The combined extracts were washed sequentially withaqueous sodium hydrogen carbonate and brine, dried over magnesiumsulfate, and concentration in vacuo. The resulting residue was purifiedby column chromatography using 25 to 100% ethyl acetate in petroleumether. Further purification by distillation afforded compound AZ1 (1.14g) in 28% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.35-1.43 (m, 3H),4.12-4.27 (m, 2H), 7.63 (d, J=570.8 Hz, 1H), 7.75-7.80 (m, 2H),7.90-7.94 (m, 2H); ³¹P NMR (CDCl₃, 161.8 MHz): δ (ppm) 22.6.

Step B: Preparation of ethyl[4-(trifluoromethyl)phenyl]-{4-(isopropoxy)-3-vinylphenyl}phosphinateBA1. To a degassed solution of ethyl4-(trifluoromethyl)-phenylphosphinate (1.00 g, 4.20 mmol) and4-bromo-1-isopropoxy-2-vinylbenzene (921 mg, 3.81 mmol) in DMF (40 mL)were added the triethylamine (1.1 mL, 7.62 mmol) andtris(dibenzylideneacetone)dipalladium (698 mg, 0.762 mmol). The mixturewas heated at 70° C. overnight. The volatiles were removed in vacuo andthe residue was purified by column chromatography using 5 to 100% ethylacetate in petroleum ether to afford compound BA1 (130 mg) as a darkgreen oil in 8.6% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.37 (d, J=6.0Hz, 6H), 1.38 (t, J=7.1 Hz, 3H), 4.07-4.17 (m, 2H), 4.63 (sept., J=6.1Hz, 1H), 5.31 (dd, J=11.2 and 1.1 Hz, 1H), 5.79 (dd, J=17.7 and 1.1 Hz,1H), 6.92 (dd, J=8.6 and 3.1 Hz, 1H), 6.99 (dd, J=17.3 and 10.8 Hz, 1H),7.59-7.66 (m, 1H), 7.67-7.72 (m, 2H), 7.87-7.96 (m, 3H); ³¹P NMR (CDCl₃,161.8 MHz): δ (ppm) 30.7.

Step C: Preparation of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy-5-(4-trifluoromethylphenylethylphosphite))phenyl]methylene-ruthenium (II) dichloride AP. Grubbs'2nd generation catalyst (277 mg, 0.326 mmol) and copper (I) chloridewere charged in a Schlenk tube and degassed. A degassed solution ofethyl[4-(trifluoromethyl)phenyl]-{4-(isopropoxy)-3-vinylphenyl}phosphinateBA1 (130 mg, 0.326 mmol) in anhydrous dichloromethane (17 mL) wastransferred via cannula to the solids. The mixture was heated at 30° C.for 70 mitt. The solvent was removed in vacuo and the residue waspurified by column chromatography using 20 to 66% ethyl acetate inpetroleum ether to afford compound AP (115 mg) as a green powder in 41%yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.26 (d, J=6.0 Hz, 6H), 1.39 (t,J=7.0 Hz, 3H), 2.38 (br s) and 2.45 (br s) (18H), 4.07-4.16 (m, 2H),4.19 (br s, 4H), 4.93 (sept., J=6.0 Hz, 1H), 6.88 (br dd, J=8.5 and 2.0Hz, 1H), 7.05 (br s, 4H), 7.27-7.47 (m, 3H), 7.86-7.99 (m, 3H), 16.4 (brs, 1H); ³¹P NMR (CDCl₃, 161.8 MHz): δ (ppm) 29.0.

Preparation of Ruthenium Complex AR

Step A: Preparation of ethyl 4-fluorophenylphosphinate AZ2. To adegassed mixture of 4-fluoro-1-iodo-benzene (25.0 g, 112.6 mmol),anilinium hypophosphite (21.5 g, 135.1 mmol) and 3-aminopropyltriethoxysilane (24.9 g, 135.1 mmol) in anhydrous acetonitrile (750 mL)were added palladium acetate (560 mg, 2.48 mmol) and1,3-bis(diphenylphosphino)propane (1.02 g, 2.48 mmol). The mixture wasrefluxed overnight. After cooling down to room temperature, the reactionmixture was concentrated in vacuo. The residue was diluted with ethylacetate and hydrochloric acid (1M) and partitioned. The aqueous layerwas further extracted with ethyl acetate and the combined extracts werewashed sequentially with aqueous sodium hydrogen carbonate and brine.The volatiles were removed in vacuo, and then the residue was purifiedby column chromatography using 50 to 100% ethyl acetate in petroleumether, affording compound AZ2 (10.1 g) as a dark orange oil in 48%yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.84 (t, J=7.1 Hz, 3H),4.08-4.24 (m, 2H), 7.20 (td, J=8.7 and 2.5 Hz, 2H), 7.58 (d, J=566.6 Hz,1H), 7.74-7.85 (m, 2H); ³¹P NMR (CDCl₃, 161.8 MHz): δ (ppm) 23.62(J=566.8 Hz).

Step B: Preparation of ethyl(4-fluorophenyl)-[4-{isopropoxy}-3-vinylphenyl]-phosphinate BA2. To adegassed mixture of 4-fluoro-phenylphosphinate AZ2 (2.07 g, 11.0 mmol)and 4-bromo-1-isopropoxy-2-vinylbenzene (2.43 g, 10.0 mmol) inacetonitrile (66 mL) were added triethylamine (3.1 mL, 22.0 mmol),palladium acetate (112 mg, 0.5 mmol), and1,1′-bis(diphenylphosphino)ferrocene (277 mg, 0.5 mmol). The mixture washeated at 68° C. for 24 hrs. The volatiles were removed in vacuo, andthe residue was purified by column chromatography using 40 to 80% ethylacetate in petroleum ether to afford 2.84 g of compound BA2 in 82%yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.36 (d, J=6.0 Hz, 6H), 1.38 (t,J=7.1 Hz, 3H), 4.02-4.15 (m, 2H), 4.62 (sept., J=6.0 Hz, 1H), 5.29 (dd,J=11.2 and 1.1 Hz, 1H), 5.78 (dd, J=17.7 and 1.4 Hz, 1H), 6.91 (dd,J=8.7 and 3.0 Hz, 1H), 6.99 (dd, J=17.4 and 10.9 Hz, 1H), 7.12 (td,J=8.8 and 2.5 Hz, 2H), 7.61 (ddd, J=11.7, 8.6 and 1.9 Hz, 1H), 7.75-7.84(m, 2H), 7.88 (dd, J=12.5 and 1.9 Hz, 1H); ³¹P NMR (CDCl₃, 161.8 MHz): δ(ppm) 30.71.

Step C: Preparation of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy-5-({4-fluoro-phenyl}ethylphosphite))phenyl]methyleneruthenium(II) dichloride AR. Grubbs' second generation catalyst (2.00 g, 2.36mmol) and copper (I) chloride (233 mg, 2.36 mmol) were charged in aSchlenk tube and degassed. A degassed solution of ethylphenyl-{4-(isopropoxy)-3-vinylphenyl}phosphinate (822 mg, 2.36 mmol) inanhydrous dichloromethane (120 mL) was transferred via cannula to thesolids. The mixture was heated at 30° C. for 60 min. The solvent wasremoved in vacuo and the residue was purified by column chromatographyusing 30 to 60% ethyl acetate in petroleum ether to afford compound AR(552 mg) in 29% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.27 (d, J=6.1Hz, 6H), 1.37 (t, J=7.0 Hz, 3H), 2.39 (br s) and 2.45 (br s) (18H),3.98-4.15 (m, 2H), 4.19 (br s, 4H), 4.93 (sept., J=6.0 Hz, 1H), 6.87 (d,J=8.2 Hz, 1H), 7.05 (br s, 4H), 7.15 (dt, J=8.6 and 2.2 Hz, 2H), 7.29(d, J=11.9 Hz, 1H), 7.72-7.81 (m, 2H), 7.91-7.99 (m, 1H), 16.44 (s, 1H);³¹P NMR (CDCl₃, 161.8 MHz): δ (ppm) 29.94.

Preparation of Ruthenium Complex AT

Step A: Preparation of ethyl 3,5-bis(trifluoromethyl)phenylphosphinateAZ3. To a degassed solution of 1-iodo-3,5-bistrifluoromethylbenzene(10.0 g, 29.4 mmol), anilinium hypophosphite (5.62 g, 35.3 mmol) and3-aminopropyl triethoxysilane (7.81 g, 35.3 mmol) in anhydrousacetonitrile (200 mL) were added palladium acetate (132 mg, 0.588 mmol,2 mol %) and 1,3-bis(diphenylphosphino)propane (267 mg, 0.647 mol, 2.2mol %). The mixture was refluxed overnight. After cooling down to roomtemperature, the reaction mixture was diluted with ethyl acetate andhydrochloric acid (IM), and then partitioned. The aqueous layer wasfurther extracted with ethyl acetate. The combined extracts were washedsequentially with aqueous sodium hydrogen carbonate and brine, and driedover sodium sulfate. The volatiles were removed in vacuo, and theresidue was purified by column chromatography using 30 to 70% ethylacetate in petroleum ether to afford compound AZ3 (4.65 g) as a cloudyoil in 52% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.45 (t, J=7.1 Hz,3H), 4.18-4.35 (m, 2H), 7.69 (d, J=579.6 Hz, 1H), 8.10 (s, 1H), 8.23 (s,1H), 8.27 (s, 1H); ³¹P NMR (CDCl₃, 161.8 MHz): δ (ppm) 19.59 (J=580.6Hz).

Step B: Preparation of ethyl[3,5-bis(trifluoromethyl)phenyl]-{4-(isopropoxy)-3-vinylphenyl}phosphinateBA3. To a degassed solution of ethyl3,5-bis(trifluoromethyl)-phenylphosphinate (3.33 g, 15.24 mmol) and4-bromo-1-isopropoxy-2-vinylbenzene (3.33 mg, 13.8 mmol) in DMF (25 mL)were added the triethylamine (3.85 mL, 27.6 mmol) andtris(dibenzylideneacetone)dipalladium (2.53 g, 2.76 mmol). The mixturewas heated in an oil bath at 70° C. overnight. The volatiles wereremoved in vacuo and the mixture was purified by column chromatographywith 20 to 70% ethyl acetate in petroleum ether to afford compound BA3(185 mg) as an oil in 2.8% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.38(dd, J=6.1 and 1.4 Hz, 6H) overlapping 1.41 (t, J=7.1 Hz, 3H), 4.11-4.21(m, 2H), 4.65 (sept., J=6.1 Hz, 1H), 5.33 (dd, J=11.2 Hz and 1.4 Hz,1H), 5.80 (dd, J=17.9 and 1.2 Hz, 1H), 6.96 (dd, J=8.6 and 3.0 Hz, 1H)overlapping 7.00 (dd, J=18.0 and 11.4 Hz, 1H), 7.63 (ddd, J=11.9, 11.9and 2.0 Hz, 1H), 7.90 (dd, J=12.7 and 2.1 Hz, 1H), 7.99 (s, 1H), 8.22(s, 1H), 8.25 (s, 1H); ³¹P NMR (CDCl₃, 161.8 MHz): δ (ppm) 28.59.

Step C: Synthesis of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy-5-(3,5-bis(trifluoromethyl)phenylethylphosphite))phenyl]methylene-ruthenium (II) dichloride AT. Grubbs'second generation catalyst (326 mg, 0.384 mmol), and copper (I) chloride(38 mg, 0.384 mmol) were charged in a Schlenk tube and degassed. Adegassed solution of ethyl[3,5-bis(trifluoromethyl)phenyl]-{4-(isopropoxy)-3-vinylphenyl}-phosphinate(179 mg, 0.384 mmol) in anhydrous dichloromethane (20 mL) wastransferred via cannula to the solids. The mixture was heated at 30° C.for 70 min. The solvent was removed in vacuo and the residue waspurified by column chromatography with 20 to 80% ethyl acetate inpetroleum ether to afford compound AT (185 mg) as a green powder in 52%yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.26 (dd, J=6.0 and 4.0 Hz, 6H),1.43 (t, J=7.0 Hz, 3H), 2.41 (br s) and 2.44 (br s) (18H), 4.07-4.25 (m,2H) overlapping 4.20 (br s, 4H), 4.94 (sept., J=6.1 Hz, 1H), 6.91 (dd,J=8.5 and 2.4 Hz, 1H), 7.06 (br s, 4H), 7.29 (dd, J=11.9 and 1.7 Hz,1H), 8.02 (br s, 1H), 8.03 (m, 1H), 8.20 (s, 1H), 8.23 (s, 1H), 16.40(s, 1H); ³¹P NMR (CDCl₃, 161.8 MHz): δ (ppm) 26.33.

Preparation of Ruthenium Complex AQ

Step A: Preparation of ethylphenyl-{4-(isopropoxy)-3-vinylphenyl}phosphinate BA4. To a degassedmixture of ethyl phenylphosphinate (1.87 g, 11.0 mmol) and4-bromo-1-isopropoxy-2-vinylbenzene (2.43 g, 10.0 mmol), which wascommercially available, in acetonitrile (66 mL) were added triethylamine(3.1 mL, 22.0 mmol), palladium acetate (112 mg, 0.5 mmol), and1,1′-bis(diphenylphosphino)ferrocene (277 mg, 0.5 mmol). The mixture wasfurther degassed and heated at 68° C. for 24 hrs. The volatiles wereremoved in vacuo, and the crude was purified by column chromatographyusing 50 to 80% ethyl acetate in petroleum ether to afford compound BA4(3.74 g) in 87% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.36 (d, J=5.7Hz, 6H), 1.37 (t, J=6.9 Hz, 3H), 4.15-4.05 (m, 2H), 4.62 (sept., J=6.0Hz, 1H), 5.28 (dd, J=11.2 and 1.4 Hz, 1H), 5.78 (dd, J=17.7 and 1.4 Hz,1H), 6.91 (dd, J=8.45 and 3.0 Hz, 1H), 6.99 (dd, J=17.9 and 11.4 Hz,1H), 7.41-7.47 (m, 2H), 7.47-7.55 (m, 1H), 7.63 (ddd. J=11.7, 8.5 and2.0 Hz, 1H), 7.79 (dd, J=12.3 and 1.4 Hz, 1H), 7.81 (dt, J=12.3 and 1.4Hz, 1H), 7.90 (dd, J=12.4 and 2.0 Hz, 1H); ³¹P NMR (CDCl₃, 161.8 MHz): δ(ppm) 32.61.

Step B: Preparation of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy-5-(phenylethylphosphite))phenyl]methyleneruthenium (II) dichloride AQ. Grubbs'second generation catalyst (2.00 g, 2.36 mmol) and copper (I) chloride(233 mg, 2.36 mmol) were charged in a Schlenk tube and degassed. Adegassed solution of ethylphenyl-{4-(isopropoxy)-3-vinylphenyl}phosphinate BA4 (778 mg, 2.36 mmol)in anhydrous dichloromethane (120 mL) was transferred via cannula to thesolids. The mixture was heated at 30° C. for 60 min. The solvent wasremoved in vacuo and the residue was purified by column chromatographyusing 40 to 100% ethyl acetate in petroleum ether to afford compound AQ(775 mg) in 41% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.27 (d, J=6.1Hz, 6H), 1.37 (t, J=7.0 Hz, 3H), 2.39 (br s) and 2.47 (br s) (18H),3.98-4.17 (m, 2H), 4.18 (br s, 4H), 4.93 (sept., J=6.0 Hz, 1H), 6.87 (d,J=7.2 Hz, 1H), 7.05 (s, 4H), 7.32 (d, J=11.9 Hz, 1H), 7.42-7.57 (m, 3H),7.77 (dd, J=12.3 and 7.2 Hz, 2H), 7.94-8.08 (m, 1H), 16.43 (s, 1H); ³¹PNMR (CDCl₃, 161.8 MHz): δ (ppm) 30.79.

Example 2 Synthesis of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(N,N-dimethylamino-ethylphosphite)phenyl]methyleneruthenium(II) dichloride C5

Ruthenium complex C5 were prepared as shown in Scheme 3.

Step A: Preparation of (4-isopropoxy-3-vinyl-phenyl) phosphonic aciddiethyl ester C1. A mixture of compound AY (928 mg, 1.1 eq.), diethylphosphite (450 μl, 1 eq), cesium carbonate (1.37 g, 1.2 eq), andtetrakis triphenylphosphine palladium (0) (202 mg, 0.05 eq) in anhydrousTHF (15 mL) was stirred under microwave irradiations at 120° C. for 15min. The reaction mixture was then filtered, washed with DCM, andconcentrated under reduced pressure. The crude material was purified bychromatography on silica gel (PE/EA) to afford compound C1 (835 mg) as atranslucid oil in 80% yield. ¹H NMR (CDCl₃, 400 MHz) δ (ppm) 1.32 (t,J=7.12 Hz, 6H), 1.38 (d, J=6.00 Hz, 6H), 4.02-4.16 (m, 4H), 4.64 (m,1H), 5.30 (dd, J=11.08 Hz and J=1.25 Hz, 1H), 5.80 (dd, J=17.66 Hz andJ=1.25 Hz, 1H), 6.93 (d, J=8.75 Hz, 1H), 7.10 (dd, J=17.50 Hz andJ=11.08 Hz, 1H), 7.64 (dd, J=8.75 Hz and J=2.55 Hz, 1H), 7.90 (d, J=2.55Hz, 1H); ³¹P NMR (CDCl₃, 161.8 MHz) δ (ppm) 19.93 (s, 1P).

Step B: Preparation of (4-isopropoxy-3-vinyl-phenyl)phosphonic acidethyl ester C2. A solution of compound C1 (1.8 g, 1 eq.) in EtOH (35 mL)and aqueous NaOH (2N, 32 mL, 12 eq.) was stirred at 80° C. for 2 hrs.The reaction mixture was then concentrated, acidified with 1N HCl to pH1, extracted with DCM, dried over Na₂SO₄, filtered, and concentratedunder reduced pressure to afford compound C2 (1.53 g) as a translucidoil in 95% yield. ¹H NMR (CDCl₃, 400 MHz) δ (ppm) 1.32 (t, J=7.12 Hz,3H), 1.38 (d, J=6.00 Hz, 6H), 4.02-4.16 (m, 2H), 4.64 (m, 1H), 5.30 (dd,J=11.08 Hz and J=1.25 Hz, 1H), 5.80 (dd, J=17.66 Hz and J=1.25 Hz, 1H),6.93 (d, J=8.75 Hz, 1H), 7.10 (dd, J=17.50 Hz and J=11.08 Hz, 1H), 7.64(dd, J=8.75 Hz and J=2.55 Hz, 1H), 7.90 (d, J=2.55 Hz, 1H); ³¹P NMR(CDCl₃, 161.8 MHz) δ (ppm) 24.90 (s, 1P).

Step C: Preparation of(4-isopropoxy-3-vinyl-phenyl)dimethyl-phosphoramidate ethyl ester C4. Toa stirred solution of compound C2 (133 mg, 1 eq.) in DCM (2 mL) with afew drops of DMF was added SOCl₂ (100 μL, 2.8 eq.) dropwise undernitrogen. The reaction mixture was allowed to stir at room temperaturefor 2 hrs and then concentrated under reduced pressure. The resultingresidue was dissolved in pyridine (2 mL) and added to a solution ofdimethylamine (2M, 0.75 mL) in THF. The mixture was stirred at roomtemperature for 16 hrs and then quenched with water. The reactionmixture was acidified with 1N HCl to pH 7, and then extracted withEtOAc. Organics were dried over Na₂SO₄, filtered, and purified bychromatography on silica gel (PE/EA) to afford compound C4 (407 mg) as awhite solid in 69% yield. ¹H NMR (CDCl₃, 400 MHz) δ (ppm) 1.36 (s, 3H),1.37 (t, J=7.15 Hz, 3H), 1.38 (s, 3H), 2.67 (s, 3H), 2.70 (s, 3H), 4.10(m, 2H), 4.62 (m, 1H), 5.30 (dd, J=11.16 Hz and J=1.50 Hz, 1H), 5.80(dd, J=17.80 Hz and J=1.50 Hz, 1H), 6.90 (dd, J=8.5 Hz and J=3.2 Hz,1H), 7.10 (dd, J=17.80 Hz and J=11.20 Hz, 1H), 7.55 (m, 1H), 7.80 (dd,J=12.90 Hz and J=2.00 Hz, 1H); ³¹P NMR (CDCl₃, 161.8 MHz) δ (ppm) 25.12(s, 1P).

Step D: Preparation of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(N,N-dimethylamino-ethylphosphite)phenyl]methyleneruthenium(II) dichloride C5. Grubbs' second generation catalyst (226 mg, 1 eq)and copper (I) chloride (26 mg, 1 eq) were charged in a Schlenk tube anddegassed. A degassed solution of compound C4 (26 mg, 21 eq.) inanhydrous dichloromethane (50 mL) was transferred via cannula to thesolid. The mixture was heated at 30° C. for 60 min. The solvent wasremoved in vacuo and the residue was purified by chromatography onsilica gel (PE/EA) to afford compound C5 (202 mg) as a green solid in100% yield. ³¹P NMR (CDCl₃, 161.8 MHz) δ (ppm) 22.88 (s, 1P); HRMS(ES+): m/z=764 (M+H⁺).

Example 3 Synthesis of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-((4-methoxy-phenyl)-ethylphosphite)phenyl]methyleneruthenium(II) dichloride D4

Ruthenium complex D4 were prepared as shown in Scheme 4.

Step A: Preparation of 4-iodo-1-isopropoxy-2-vinyl-benzene D1. A mixtureof compound AY (2.56 g, 1 eq.), sodium iodide (3.18 g, 2 eq.), copperiodide (100 mg, 0.05 eq.), and N,N′-dimethylcyclohexene-1,2-diamine (170μL, 0.1 eq.) in dioxane (10 mL) was refluxed under nitrogen for 16 hrs.Aqueous NH₃ solution (20%, 100 mL) was added. The mixture was thenpoured into H₂O. Organics were separated, concentrated under reducedpressure, and purified by chromatography on silica gel (PE/EA) to affordcompound D1 (1.83 g) as a yellow oil in 60% yield. ¹H NMR (CDCl₃, 400MHz) δ (ppm) 1.33 (s, 3H), 1.35 (s, 3H), 4.50 (m, 1H), 5.30 (dd, J=11.15Hz, J=1.30 Hz, 1H), 6.70 (dd, J=17.80 Hz, J=1.30 Hz, 1H), 6.65 (d,J=8.80 Hz, 1H), 6.90-6.97 (dd, J=17.80 Hz, J=11.20 Hz, 1H), 7.47 (dd,J=8.80 Hz, J=2.20 Hz, 1H), 7.75 (d, J=2.20 Hz, 1H).

Step B: Preparation of (4-isopropoxy-3-vinyl-phenyl)-phosphinic acidethyl ester D2. A mixture of compound D1 (4.85 g, 1 eq.), aniliniumhypophosphite (3.21 g, 1.2 eq.), (3-aminopropyl)triethoxysilane (4.75ml, 1.2 eq.), palladium acetate (75 mg, 0.02 eq.), and1,3-bis(diphenylphosphino)propane (139 mg, 0.02 eq.) in acetonitrile(200 mL) was refluxed for 16 hrs. The reaction mixture was filtered,concentrated under reduced pressure, and purified by chromatography onsilica gel (PE/EA) to afford compound D2 (1.97 g) as a yellow oil in 46%yield. ¹H NMR (CDCl₃, 400 MHz) δ (ppm) 1.33 (s, 3H), 1.35 (s, 3H), 4.50(m, 1H), 4.15 (m, 3H), 5.30 (dd, J=11.15 Hz, J=1.30 Hz, 1H), 6.70 (dd,J=17.80 Hz, J=1.30 Hz, 1H), 6.65 (d, J=8.80 Hz, 1H), 6.80 (m, 2H),6.90-6.97 (dd, J=17.80 Hz, J=11.20 Hz, 1H), 7.47 (dd, J=8.80 Hz, J=2.20Hz, 1H), 7.75 (d, J=2.20 Hz, 1H), 8.27 (s, 1H); ³¹P NMR (CDCl₃, 161.8MHz) δ (ppm) 24.90 (s, 1P).

Step C: Preparation of (4-isopropoxy-3-vinyl-phenyl)-(4-methoxy-phenyl)phosphinic acid ethyl ester D3. A mixture of compound D2 (650 mg, 1eq.), 4-iodoanisole (778 mg, 1.3 eq.), TEA (1.08 mL, 3 eq.), andPd(PPh₃)₄ (295 mg, 0.1 eq.) in toluene (6.4 mL) was stirred at 110° C.for 16 hrs under nitrogen. The reaction mixture was filtered through acelite pad, washed with DCM, concentrated under reduced pressure, andpurified by chromatography on silica gel (PE/EA) to afford compound D3(1.97 g) as an orange oil in 58% yield. ¹H NMR (CDCl₃, 400 MHz) δ (ppm)1.33 (s, 3H), 1.35 (s, 3H), 3.84 (s, 3H), 4.50 (m, 1H), 4.15 (m, 3H),5.30 (dd, J=11.15 Hz and J=1.30 Hz, 1H), 6.70 (dd, J=17.80 Hz and J=1.30Hz, 1H), 6.65 (d, J=8.80 Hz, 1H), 6.80 (m, 2H), 6.90-6.97 (dd, J=17.80Hz and J=11.20 Hz, 1H), 7.47 (dd, J=8.80 Hz and J=2.20 Hz, 1H), 7.75 (d,J=2.20 Hz, 1H), 7.80 (m, 4H); ³¹P NMR (CDCl₃, 161.8 MHz) δ (ppm) 32.71(s, 1P).

Step D: Preparation of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-((4-methoxy-phenyl)-ethylphosphite)phenyl]methyleneruthenium(II) dichloride D4. Compound D4 was synthesized from compound D4 as adark solid in 35% yield according to the procedure as described forcompound CS. ³¹P NMR (CDCl₃, 161.8 MHz) δ (ppm) 30.52 (s, 1P); HRMS(ES+): m/z=827 (M+H⁺).

Example 4 Synthesis of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(phenyl-ethylphosphoramidate)phenyl]methyleneruthenium(II) dichloride E6

Ruthenium complex E6 were prepared as shown in Scheme 5.

Step A: Preparation of 2-isopropoxy-5-nitro-benzaldehyde E1. Compound E1was synthesized from 2-hydroxy-5-nitro-benzaldehyde as a yellow solid in39% yield according to the procedure as described for compound AX. ¹HNMR (CDCl₃, 400 MHz) δ (ppm) 1.47 (s, 3H), 1.49 (s, 3H), 4.84 (m, 1H),7.09 (d, J=9.20 Hz, 1H), 8.40 (dd, J=9.33 Hz and J=2.93 Hz, 1H), 8.70(d, J=3.04 Hz, 1H), 10.46 (s, 1H).

Step B: Preparation of 1-isopropoxy-4-nitro-2-vinylbenzene E2. CompoundE2 was synthesized from compound E1 as a yellow oil in 63% yieldaccording to the procedure as described for compound AY. ¹H NMR (CDCl₃,400 MHz) δ (ppm) 1.47 (s, 3H), 1.49 (s, 3H), 4.84 (m, 1H), 5.39 (dd,J=11.02 Hz and J=1.00 Hz, 1H), 5.89 (dd, J=17.70 Hz and J=1.00 Hz, 1H),7.09 (d, J=9.20 Hz, 1H), 8.40 (dd, J=9.33 Hz and J=2.93 Hz, 1H), 8.12(dd, J=9.22 Hz and J=2.89 Hz, 1H), 8.37 (d, J=3.04 Hz, 1H).

Step C: Preparation of 4-isopropoxy-3-phenylamine E3. To a stirredsolution of compound E2 (114 mg, 1 eq.) in acetic acid (5.5 mL) wasadded zinc dust (360 mg, 10 eq.). The reaction mixture was stirred atroom temperature for 50 min. The mixture was then filtered, concentratedunder reduced pressure, and purified by chromatography on silica gel(PE/EA) to afford compound E3 (84 mg) as a yellow oil in 86% yield. ¹HNMR (CDCl₃, 400 MHz) δ (ppm) 1.29 (s, 3H), 1.31 (s, 3H), 4.16 (brs, 2H),4.34 (m, 1H), 5.23 (dd, J=11.02 Hz and J=1.00 Hz, 1H), 5.69 (dd, J=17.70Hz and J=1.00 Hz, 1H), 6.60 (dd, J=8.50 Hz and J=2.80 Hz, 1H), 6.77 (d,J=8.50 Hz, 1H), 6.87 (d, J=3.10 Hz, 1H), 7.01 (dd, J=17.80 Hz andJ=11.20 Hz, 1H).

Step D: Preparation of phenyl phosphinic acid ethyl ester E4. Phenyldiethylphosphonate (2.05 g, 1 eq.) was stirred in aqueous NaOH solution(2N, 55 mL, 12 eq.) and EtOH (55 mL, 12 eq.) at 80° C. for 3 hrs. Thereaction mixture was then concentrated, acidified to pH 1 with 1N HCl,extracted with DCM, and concentrated under reduced pressure to affordcompound E4 as a transparent oil in 90% yield. ¹H NMR (CDCl₃, 400 MHz) δ(ppm) 1.30 (t, J=7.17 Hz, 3H), 4.08 (q, J=7.17 Hz, 2H), 7.43 (m, 2H),7.53 (t, J=7.22 Hz, 1H), 7.81 (m, 2H), 11.3 (brs, 1H); ³¹P NMR (CDCl₃,161.8 MHz) δ (ppm) 20.96 (s, 1P).

Step E: Preparation of N-(phenyl-phosphinic acid ethylester)-4-isopropoxy-3-vinyl-aniline E5. Compound E5 was synthesized fromcompounds E3 and E4 as a yellow oil in 53% yield according to theprocedure as described for compound C4. ¹H NMR (CDCl₃, 400 MHz) δ (ppm)1.26 (s, 3H), 1.28 (s, 3H), 1.34 (t, J=7.17 Hz, 3H), 4.08 (q, J=7.17 Hz,2H), 4.30 (m, 1H), 5.12 (m, 2H), 5.60 (d, J=17.20 Hz, 1H), 6.70 (d,J=8.80 Hz, 1H), 6.70 (dd, J=8.80 Hz and J=2.80 Hz, 1H), 6.95 (dd,J=17.20 Hz and J=11.09 Hz, 1H), 7.10 (d, J=2.80 Hz, 1H), 7.43 (m, 2H),7.52 (m, 1H), 7.80 (dd, J=13.15 Hz and J=7.20 Hz, 1H); ³¹P NMR (CDCl₃,161.8 MHz) δ (ppm) 17.05 (s, 1P).

Step F: Preparation of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(phenyl-ethylphosphoramidate)phenyl]methyleneruthenium(II) dichloride E6. Compound E6 was synthesized from compound E5 as agreen solid in 74% yield according to the procedure as described forcompound C5. ³¹P NMR (CDCl₃, 161.8 MHz) δ (ppm) 17.01 (s, 1P); HRMS(ES+): m/z=811 (M+H⁺).

Example 5 Synthesis of1,3-bis(2-methylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(phenyl-ethylphosphite)phenyl]methyleneruthenium(II) dichloride G2

Ruthenium complex G2 was prepared as shown in Scheme 6.

Preparation of1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(i-propoxy)-5-(phenyl-ethylphosphite)phenyl]methyleneruthenium(II) dichloride G2. Compound G2 was synthesized from compounds BA4 andG1 as a dark solid in 33% yield according to the procedure as describedfor compound C5. ³¹P NMR (CDCl₃, 161.8 MHz) δ (ppm) 30.86 (s, 1P); HRMS(ES+): m/z=740 (M+H⁺).

Example 6 Ring Closure Metathesis

Catalytic activity of Ru catalysts AP, AQ, AR, AT, C5, D4, E6, and G2was evaluated using seven olefin substrates as shown in Schemes 7 and 8,along with five other Ru catalysts, AO, AS, AU, AV, and AW, as shown inScheme 9.

A. Synthesis of Substratesa. Syntheses of Compounds BB, BD, and BF

Compound BB is a commercially available product. Compounds BD and BFwere prepared according to Kotora et al., J. Am. Chem. Soc., 2004,126:10222-10223; and Zhang et al., J. Am. Chem. Soc., 2004, 126:74-75.

b. Syntheses of Compounds BH and BI

Compound BI was synthesized according to Scheme 10.

Step A: Preparation of (2S,4R)-tert-butyl2-(N-(hex-5-enyl)-N-methyl-carbamoyl)-4-hydroxypyrrolidine-1-carboxylate48. To a cold solution of cis-N-Boc-4-hydroxy-L-proline (10 g, 1 eq.),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate(TBTU 15.5 g, 1.12 eq.) and N-methylhex-5-en-1-amine tosylate salt 32a(13.6 g, 1.1 eq.), which was prepared according to Scheme 13 asdescribed herein, in DMF (80 mL) containing DIPEA (29.4 mL, 3.9 eq.) wasadded dropwise under nitrogen at 0° C. The reaction mixture was stirredovernight at room temperature, and then quenched with water andextracted with diethyl ether. The organic layer was washed with brine,dried over magnesium sulfate, and concentrated under reduced pressure.The residue was purified by chromatography on silica gel to yieldcompound 48 as a rose powder in 95% yield. ¹H NMR (DMSO-d₆, 400 MHz): δ(ppm) 1.29-1.3 (m, 9H), 1.33-1.55 (m, 4H), 1.70-1.80 (m, 1H), 1.97-2.12(m, 3H), 2.77-2.97 (m, 3H), 3.15-3.40 (m, 4H), 4.22 (br s, 1H),4.50-4.62 (m, 1H), 4.90-5.04 (m, 3H), 5.71-5.83 (m, 1H); MS (ESI⁺):m/z=327 (MH⁺).

Step B: Preparation of(2S,4R)—N-(hex-5-enyl)-4-hydroxy-N-methyl-pyrrolidine-2-carboxamide 49.Trifluoroacetic acid was added dropwise to a solution of compound 48 (1g, 1 eq.) in DCM (10 mL). The reaction mixture was stirred for 3 hrs atroom temperature, and then trifluoroacetic acid was removed underreduced pressure. The residue was co-evaporated with toluene to yieldcompound 49 as pale yellow oil in quantitative yield. MS (ESI⁺): m/z=227(MIT).

Step C: Preparation of(1R)-1-{[2(S)-(hex-5-enyl-methyl-carbamoyl)-4(R)-hydroxy-pyrrolidine-N-carbonyl]amino}-2(R)-vinyl-cyclopropanecarboxylicacid ethyl ester 50. Triethylamine (1.3 mL, 3 eq.) was added at roomtemperature under nitrogen to a mixture of1-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropyl-carbamoyl)-3-methyl-1H-imidazol-3-iumiodide 34 (0.7 g, 1 eq.) and compound 49 (1.2 g, 1 eq.) in DCM (15 mL).The reaction mixture was stirred overnight at room temperature and thenquenched with 1M aqueous hydrochloric acid. The organic layer was driedover sodium sulfate and concentrated under reduced pressure. The residuewas purified by chromatography on silica gel to yield compound 50 as awhite solid in 70% yield. ¹H NMR (DMSO-d₆, 400 MHz): δ (ppm) 1.10-1.14(td, J=7.07 and 2.01 Hz, 3H), 1.15-1.17 (m, 1H), 1.22-1.30 (m, 1H),1.33-1.41 (m, 2H), 1.42-1.50 (m, 1H), 1.54-1.57 (m, 1H), 1.71-1.79 (m,1H), 1.97-2.07 (m, 4H), 2.74 (s, 1H), 2.97 (s, 2H), 3.11 (d, J=10.24 Hz,1H), 3.15-3.21 (m, 1H), 3.43-3.48 (m, 1H), 3.91-4.07 (m, 2H), 4.29-4.30(m, 1H), 4.65-4.69 (d, J=6.50 Hz, 1H), 4.90-4.96 (m, 3H), 5.00-5.06 (m,2H), 5.19-5.25 (dd, J=17.04 and 6.50 Hz, 1H), 5.51-5.61 (m, 1H),5.71-5.83 (m, 1H), 7.08 (s, 1H); MS (ESI⁻): m/z=406 (MH⁻).

Step D: Preparation of(3R,5S)-1-((1R,2S)-1-(ethoxycarbonyl)-2-vinyl-cyclopropylcarbamoyl)-5-(hex-5-enyl(methyl)carbamoyl)pyrrolidin-3-yl-4-nitrobenzoateBI. To a solution of 4-nitrobenzoic acid (3.1 g, 1.5 eq) in CH₂Cl₂ (61mL) were added dropwise 3.1 mL oxalyl chloride (3 eq), followed by 60 μLDMF. The reaction mixture was stirred at room temperature for 2 hrs andconcentrated in vacuo. A solution of the resulting solid in CH₂Cl₂ (30mL) was added dropwise to a solution of compound 50 (5.0 g, 1 eq) andtriethylamine (3.4 mL, 2 eq) in CH₂Cl₂ (30 mL). The reaction mixture wasstirred at room temperature for 2 hrs, and then washed with water and asaturated aqueous solution of sodium carbonate. The aqueous layer wasextracted with CH₂Cl₂. The combined organic phases were dried on sodiumsulphate, filtered, and concentrated to dryness. Recrystallisation withTBME gave compound BI as a yellow powder, and the filtrate was submittedto flash chromatography using CH₂Cl₂/MeOH as an eluant, affording atotal of 6.42 g of compound BI in 93% yield. ¹H NMR (CDCl₃, 400 MHz) δ(ppm) 1.23 (m, 3H), 1.36-1.61 (m, MI), 1.69 (m, 1H), 1.86 (td, J=5.1 and7.8 Hz, 1H), 2.05-2.19 (m, 3H), 2.35-2.50 (m, 2H), 2.95 and 3.15 (2s,rotamers, 3H), 3.21 and 3.80 (2m, rotamers, 1H), 3.38 (m, 1H), 3.61 (m,1H), 4.09 (m, 2H), 4.21 (m, 1H), 4.94-5.00 (m, 1H), 5.05 (br d, 10.3 Hz,2H), 5.10 (dd, J=1.30 and 10.2 Hz, 1H), 5.27 (d, J=17.0 Hz, 1H),5.68-5.84 (m, 3H), 8.20 (d, J=8.8 Hz, 2H), 8.31 (d, J=8.8 Hz, 2H).

Compound BH (white powder) was synthesized using the same procedure ascompound 50. ¹H NMR (CDCl₃, 400 MHz) δ 1.34-1.46 (m, 2H), 1.49-1.57 (m,3H), 1.70 (s, 2H), 1.86 (td, J=8.0 and 5.4 Hz, 1H), 2.03-2.28 (m, 6H),2.92 and 3.11 (2s, rotamers, 3H), 3.27-3.44 (m, 2H), 3.69 (s, 3H), 3.79(m, J=5.1 and 4.5 Hz, 1H), 4.71 (br s, 1H), 4.90-4.97 (m, 1H), 4.97-5.05(m, 1H), 5.09 (dd, J=10.3 and 1.5 Hz, 1H), 5.20 (br s, 1H), 5.27 (dd,J=17.1 and 1.0 Hz, 1H), 5.67-5.85 (m, 2H).

c. Syntheses of Compounds BK and BM

Compounds BK and BM were prepared according to Scheme 11.

Step A: Preparation of (2S,4S)-1-tert-butyl 2-methyl4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)pyrrolidine-1,2-dicarboxylateBQ. The7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-ol BO(10.0 g, 1 eq.), the N-Boc-trans-4-hydroxyproline methyl ester BP (7.20g, 1 eq.), and the triphenylphosphine (11.56 g, 1.5 eq.) in suspensionin THF (250 mL) under N₂ were cooled down to 0° C. The DIAD (8.70 mL,1.5 eq.) was added dropwise. The reaction mixture was allowed to warm upand stir at room temperature for 1.25 hrs, then cooled again at 0° C.and additional 1 more eq. of DIAD was added. The reaction mixture wasstirred for 2 hrs at room temperature, and then concentrated in vacuo to50 mL. Water and ethyl acetate were added and the phases were separated.The aqueous layer was further extracted with ethyl acetate. The organiclayer was washed with brine, dried over magnesium sulfate, andconcentrated under reduced pressure. The residue was purified bychromatography on silica gel to yield compound BQ (16.75 g, 87% purity).MS (ESI, EI⁺) m/z=568.3 (MH⁺); 626.5 (M+OAc⁻).

Step B: Preparation of(2S,4S)-4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)-thiazol-2-yl)quinolin-4-yloxy)pyrrolidine-2-carboxylicacid hydrochloride salt BR. Compound BQ (16.75 g, 1 eq.) in 440 mL ofaqueous 6M HCl solution was allowed to stir at 40° C. overnight. Thesolution was washed with DCM, and the aqueous layer was concentratedunder reduced pressure and lyophilized to afford compound BR (12.70 g)as a yellow solid in quantitative yield. ¹H NMR (CDCl₃, 400 MHz) δ (ppm)2.58 (s, 3H), 2.85-2.90 (m, 2H), 3.82-3.92 (m, 2H), 3.99 (s, 3H), 4.73(dd, J=8.2 and 4.4 Hz, 1H), 5.69-5.73 (m, 1H), 7.42 (d, J=9.4 Hz, 1H),7.63 (s, 1H), 8.00 (d, J=9.4 Hz, 1H), 8.33 (s, 1H).

Step C: Preparation of(2S,4S)-4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)-thiazol-2-yl)quinolin-4-yloxy)-1-((1R,2S)-1-(methoxycarbonyl)-2-vinylcyclopropyl-carbamoyl)pyrrolidine-2-carboxylicacid BS. To a suspension of compound BR (9.70 g, 1 eq.) in DCM (230 mL)was added the triethylamine (10.9 mL, 3 eq.), and after 15 minutes,compound BT, which was prepared according to Scheme 12 as describedherein, in solution in DCM (70 mL). The reaction mixture was allowed tostir at room temperature overnight. Water was added and the aqueouslayer was extracted with DCM. The organic layer was washed with brine,dried over magnesium sulfate, and concentrated under reduced pressure.The residue was purified by chromatography on silica gel to yieldcompound BS (14.62 g) as a yellow solid in 91% yield. ¹H NMR (CDCl₃, 400MHz) δ (ppm) 1.47-1.52 (m, 1H), 1.80-1.86 (m, 1H), 2.09-2.20 (m, 1H),2.37-2.50 (m, 4H), 3.00-3.16 (m, 1H), 3.56 (s, 3H), 3.70-3.77 (m, 1H),3.85 (s, 3H), 4.61-4.71 (m, 1H), 5.04 (d, J=9.9 Hz, 1H), 5.15-5.26 (m,2H), 5.57-5.76 (m, 2H), 7.12 (d, J=9.4 Hz, 1H), 7.16 (s, 1H), 7.74 (d,J=9.4 Hz, 1H), 7.16 (s, 1H).

Step D: Preparation of (1R,2S)-methyl1-((2S,4S)-2-(hex-5-enyl(methyl)-carbamoyl)-4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)-pyrrolidine-1-carboxamido)-2-vinylcyclopropanecarboxylateBK. A solution of compound BS (3.74 g, 1 eq.), N-methylhex-5-en-1-aminetosylate salt 32a (1.57 g, 1.1 eq.), which was prepared according toScheme 13 as described herein, andO-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate(TBTU, 2.32 g, 1.2 eq.) in DCM (60 mL) was stirred at room temperaturefor 40 min. The reaction mixture was then cooled down to 0° C. and DIPEA(4.10 mL, 3.9 eq.) was added dropwise. The reaction mixture was allowedto warm up and stir at room temperature for 2 hrs. Water was added andthe aqueous layer was extracted with DCM. The organic layer was washedwith brine, dried over magnesium sulfate, and concentrated under reducedpressure. The residue was purified by chromatography on silica gel toyield compound BK (4.30 g) as a yellow solid in quantitative yield). ¹HNMR (CDCl₃, 400 MHz) δ (ppm) 1.18-1.45 (m, 4H), 1.48-1.58 (m, 1H),1.81-1.90 (m, 2H), 2.05 (m, J=7.6 Hz, 1H), 2.21 (se, J=7.3 Hz, 1H),2.27-2.36 (m, 1H), 2.67 (s, 3H), 2.88 and 3.00 (2s, rotamers, 3H),3.06-3.14 and 3.20-3.29 (2m, rotamers, 1H), 3.33-3.42 and 3.49-3.58 (2m,rotamers, 1H), 3.71 (s, 3H), 3.92 (td, J=10.1 and 3.8 Hz, 1H), 3.98 and3.99 (2s, rotamers, 3H), 4.06-4.13 (m, 1H), 4.83-5.03 (m, 3H), 5.10 (d,J=10.5 Hz, 1H), 5.14 (dd, J=10.3 and 1.2 Hz, 1H), 5.21 (s, 1H),5.26-5.34 (m, 1H), 5.40-5.46 (m, 1H), 5.58-5.80 (m, 2H), 7.24-7.28 (m,1H), 7.45 (d, J=7.1 Hz, 1H), 7.86 (s, 1H), 8.05 (t, J=8.1 Hz, 1H); MS(ESI, EI⁺) m/z=716.2 (MH⁺).

Step E: Preparation of (1R,2S)-1-((2S,4S)-2-(hex-5-enyl(methyl)carbamoyl)-4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)pyrrolidine-1-carboxamido)-2-vinylcyclopropanecarboxylicacid. Compound BN (yellow solid) was synthesized in quantitative yieldfrom compound BK (4.30 g, 1 eq) and LiOH (290 mg, 2 eq). MS (ESI, EI⁺)m/z=702.4 (MH⁺).

Step F: Preparation of(2S,4S)—N²-(hex-5-enyl)-4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)-N²-methyl-N¹-((1R,2S)-1-(1-methyl-cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-1,2-dicarboxamide.Compound BM (white solid) was synthesized from compound BN (4.22 g, 1eq) and 1-methylcyclopropylsulfonamide (3.25 g, 4 eq) in 31% yieldaccording to the following procedure: Under nitrogen, a solution ofcompound BN and EDCI (2 eq.) in dry dichloromethane (5 mL) was stirredat room temperature for 2 hours, 1-Methylcyclopropyl-sulfonamide (4 eq.)and DBU (2 eq.) were then added under nitrogen and the reaction mixturewas stirred for additional 20 hours. Dichloromethane and water wereadded and the two layers separated. The organic layer was washed withwater (three times) and brine, then dried over Na₂SO₄, filtered andconcentrated under reduced pressure. The residue was purified bychromatography on silica gel to yield compound BM. ¹H NMR (CDCl₃, 400MHz) δ (ppm) 0.74-0.86 (m, 2H), 1.11-1.21 (m, 2H), 1.30-1.40 (m, 3H),1.50 (s, 3H), 1.60-1.68 (m, 3H), 1.78 (q. J=6.0 Hz, 1H), 1.88-1.94 (m,1H), 2.00-2.08 (m, 1H), 2.22 (q, J=8.7 Hz, 1H), 2.33 (dd, J=14.0 and 2.1Hz, 1H), 2.67 (s, 3H), 2.78-2.82 (m, 1H), 2.87 and 2.97 (2s, rotamers,3H), 3.15-3.36 (m, 1H), 3.58-3.68 (m, 1H), 3.90-4.01 (m, 5H), 4.82-4.91(m, 1H), 4.92-5.01 (m, 2H), 5.11 (d, J=10.2 Hz, 1H), 5.25-5.35 (m, 2H),5.46-5.51 (m, 1H), 5.54-5.76 (m, 2H), 7.25-7.30 (m, 1H), 7.46 (d, J=7.0Hz, 1H), 7.87 (s, 1H), 8.02 (t, J=10.1 Hz, 1H); MS (ESI, EE) m/z=819.2(MH⁺).

d. Synthesis of Compound BT

Preparation of (1R,2S)-methyl1-(1H-imidazole-1-carboxamido)-2-vinylcyclopropanecarboxylate BT.Compound BT was prepared according to Scheme 12. To a suspension of(1R,2S)-methyl 1-amino-2-vinylcyclopropanecarboxylate tosylate salt(25.0 g, 1 eq.) in THF (150 mL) at 50° C. were added CDI (14.24 g, 1.1eq.) and TEA (12.27 mL, 1.1 eq.). The reaction mixture was then refluxedovernight. The solvent was removed under reduced pressure. The residuewas dissolved in EtOAc, and washed with water. The organic layer wasdried over sodium sulfate and concentrated. The residue was trituratedin Et₂O to afford compound BT (15.24 g, purity 80%) as a white solid. ¹HNMR (CDCl₃, 400 MHz): δ (ppm) 1.63 (dd, J=5.8 and 9.7 Hz, 1H), 1.96 (dd,J=5.8 and 8.4 Hz, 1H), 2.30 (q, J=8.9 Hz, 1H), 3.73 (s, 3H), 5.16 (d,J=10.0 Hz, 1H), 5.28 (d, J=17.0 Hz, 1H), 5.69-5.81 (m, 1H), 7.03 (s,1H), 7.50 (s, 1H), 8.24 (s, 1H), 8.57 (s, 1H).

e. Synthesis of Compound 32a

The synthesis of N-methyl-o-alkenyl-1-amine tosylate salt 32a is shownin Scheme 13.

Step A: Preparation of 2,2,2-trifluoro-N-(hex-5-enyl)-N-methylacetamide31a. Sodium hydride (60% dispersion in mineral oil, 31.5 g, 1.28 eq.)was slowly added under nitrogen atmosphere to a solution ofN-methyl-2,2,2-trifluoroacetamide (100 g, 1.28 eq.) in DMF (500 mL) at0° C. The reaction mixture was stiffed for 90 min at 0° C., and then6-bromo-1-hexene (100 g, 1 eq.) was added dropwise over 45 min. Thereaction mixture was allowed to warm up to room temperature, and stirredfor 3 days at room temperature. The reaction mixture was then pouredinto water and extracted tree time with EtOAc. The combined organicslayers were dried over anhydrous sodium sulphate and concentrated underreduced pressure. The residue was purified by flash chromatography onsilica gel to produce compound 31a as colorless oil in 56% yield. ¹H NMR(DMSO-d₆, 400 MHz) δ (ppm) 1.27-1.38 (m, 2H), 1.48-1.60 (m, 2H),2.00-2.06 (m, 2H), 2.93-3.07 (2m, 3H), 3.35-3.40 (m, 2H), 4.92-5.04 (m,2H), 5.73-5.83 (m, 1H).

Step B: Preparation of N-methylhex-5-en-1-amine tosylate salt 32a. Atroom temperature, compound 31a (71.88 g, 1 eq.) and p-toluene sulfonicacid (74.4 g, 1.2 eq.) were dissolved in MeOH (640 mL). The reactionmixture was refluxed for 7 days. The solvent was then removed undervacuum, and the residue was recrystallized in acetone. The product wasisolated by filtration and dried over P₂O₅ to give compound 32a as awhite powder in 76% yield. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.38 (q,J=7.76 Hz, 2H), 1.71 (q, J=7.76 Hz, 2H), 1.99 (q, J=6.98 Hz, 2H), 2.38(s, 3H), 2.70 (t, J=5.17 Hz, 3H), 2.87-2.93 (m, 4.92-4.99 (m, 2H),5.67-5.73 (m, 1H), 7.20 (d, J=7.76 Hz, 2H), 7.75 (d, J=7.76 Hz, 2H),8.62 (br s, 2H).

B. Ring Closure Metathesis

All reactions were performed in 1,2-dichloroethane at 0.005 M with N₂bubbling through the reaction mixture. For the substrates depicted inScheme 7, the RCM reactions were carried out on a 100-mg scale; whereasfor the substrates depicted in Scheme 8, the typical scale of thereaction was 200-250 mg. The catalyst was added in solution in 0.5 mL ofDCE, in the pre-heated reaction mixture. The conversion of the startingmaterial was followed via TLC and/or HPLC. Products are isolated afterflash chromatography (note: compound III was stirred with charcoal andfiltered on celite prior to purification).

The experimental results of catalytic activity for the differentcatalysts are listed in Tables 1 to 7, respectively.

TABLE 1 Compound BC Isolated Time Entry Catalyst Temperature Catalystloading yield (%) (hrs) 1 AO 40° C. 1.5% + 1.5% (1 hr) 99 2.0 2 AP 40°C. 1.5% + 1.5% (1 hr) 87 2.5 3 AQ 40° C. 1.5% + 1.5% (1 hr) 87 2.5 4 AR40° C. 1.5% + 1.5% (1 hr) + 93 3.0 1% (2.2 hrs) 5 AS 40° C. 1.5% + 1.5%(1 hr) + 91 3.0 1% (2.2 hrs) 6 AT 40° C. 1.5% + 1.5% (1 hr) + 82 3.0 1%(2.2 hrs) 7 C5 40° C. 1.5% + 1.5% (1 hr) 94 2.5 8 D4 40° C. 1.5% + 1.5%(1 hr) 93 2.5 9 E6 40° C. 1.5% + 1.5% (1 hr) 85 2.5 10 G2 40° C. 1.5% +1.5% (1 hr) 71 2.5

Synthesis of diethyl cyclopent-3-ene-1,1-dicarboxylate BC. ¹H NMR(CDCl₃, 400 MHz): δ (ppm) 1.18 (t, J=7.2 Hz, 6H), 2.94 (s, 4H), 4.13 (q,J=7.2 Hz, 4H), 5.54 (s, 2H); MS (ESI, EE): m/z=213.0 (MH⁺).

Synthesis of diethyl 3-methylcyclopent-3-ene-1,1-dicarboxylate BE. ¹HNMR (CDCl₃, 400 MHz): δ (ppm) 1.66 (s, 3H), 2.42 (s, 3H), 3.97 (m, 2H),4.07 (m, 2H), 5.25 (m, 1H), 7.32 (d, J=8.2 Hz, 2H), 7.72 (d, J=8.2 Hz,2H); MS (ESI, EI⁺): m/z=238.1 (MH⁺).

TABLE 2 Compound BE Isolated Time Entry Catalyst Temperature Catalystloading yield (%) (hrs) 1 AO 40° C. 1.5% + 1.5% (1 hr) + 1.5% (2.5 hrs)99 4 2 AP 40° C. 1.5% + 1.5% (1 hr) + 1.5% (2.5 hrs) 91 4 3 AQ 40° C.1.5% + 1.5% (1 hr) + 1.5% (2.5 hrs) 97 4 4 AR 40° C. 1.5% + 1.5% (1hr) + 1.5% (2.5 hrs) 93 3.5 5 AS 40° C. 1.5% + 1.5% (1 hr) + 1.5% (2.5hrs) 74 3.5 6 AT 40° C. 1.5% + 1.5% (1 hr) + 1.5% (2.5 hrs) 81 3.5 7 C540° C. 1.5% + 1.5% (1 hr) + 1.5% (2.5 hrs) 99 3.5 8 D4 40° C. 1.5% +1.5% (1 hr) + 1.5% (2.5 hrs) 96 3.5 9 E6 40° C. 1.5% + 1.5% (1 hr) +1.5% (2.5 hrs) 93 3.5 10 G2 40° C. 1.5% + 1.5% (1 hr) + 1.5% (2.5 hrs)70 3.5

TABLE 3 Compound BG Isolated Time Entry Catalyst Temperature Catalystloading yield (%) (hrs) 1 AO 40° C. 1.5% + 1.5% (1 hr) 95 2.5 2 AP 40°C. 1.5% + 1.5% (1 hr) 85 3.5 3 AQ 40° C. 1.5% + 1.5% (1 hr) + 0.7% (2.5hrs) 85 3.5 4 AR 40° C. 1.5% + 1.5% (1 hr) + 0.7% (2.5 hrs) 79 3.5 5 AS40° C. 1.5% + 1.5% (1 hr) + 0.7% (2.5 hrs) 93 3.5 6 AT 40° C. 1.5% +1.5% (1 hr) + 0.7% (2.5 hrs) 93 3.5 7 C5 40° C. 1.5% + 1.5% (1 hr) +0.7% (2.5 hrs) 92 3.5 8 D4 40° C. 1.5% + 1.5% (1 hr) + 0.7% (2.5 hrs) 923.5 9 E6 40° C. 1.5% + 1.5% (1 hr) + 0.7% (2.5 hrs) 87 3.5 10 G2 40° C.1.5% + 1.5% (1 hr) + 0.7% (2.5 hrs) 85 3.5

Synthesis of (1aR,6R,7aS,15aS,Z)-methyl6-hydroxy-9-methyl-3,8-dioxo-1a,2,3,5,6,7,7a,8,9,10,11,12,13,15a-tetradecahydro-1H-cyclopropa[m]pyrrolo[1,2-c][1,3,6]triazacyclotetradecine-1a-carboxylateD.

Synthesis of 3-methyl-1-tosyl-2,5-dihydro-1H-pyrrole BG. ¹H NMR (CDCl₃,400 MHz): δ (ppm) 1.66 (s, 3H), 2.42 (s, 3H), 3.97 (m, 2H), 4.07 (m,2H), 5.25 (m, 1H), 7.32 (d, J=8.2 Hz, 2H), 7.72 (d, J=8.2 Hz, 2H); MS(ESI, EI⁺): m/z=238.1 (MH⁺).

TABLE 4 Compound D Isolated Time Entry Catalyst Temperature Catalystloading yield (%) (hr) 1 AO 80° C. 2% + 1% (1.5 hrs) 51 2.5 2 AP 80° C.2% + 1% (1.5 hrs) 44 3.0 3 AQ 80° C. 2% + 1% (1.5 hrs) 56 2.5 4 AR 80°C. 2% + 1% (1.5 hrs) 47 2.5 5 AS 80° C. 2% + 1% (1.5 hrs) 50 2.5 6 AT80° C. 2% + 1% (1.5 hrs) 53 3.0 7 AU 80° C. 2% + 1% (1.5 hrs) 50 2.5 8C5 80° C. 2% + 1% (1.5 hrs) 52 3 9 D4 80° C. 2% + 1% (1.5 hrs) 44 3 10E6 80° C. 2% + 1% (1.5 hrs) 45 3 11 G2 80° C. 2% + 1% (1.5 hrs) 11 2.5

TABLE 5 Compound BJ Isolated Time Entry Catalyst Temperature Catalystloading yield (%) (hrs) 1 AO 80° C. 2% + 2% (20 min) 65 0.67 2 AP 80° C.2% + 2% (20 min) + 78 1.0 1% (40 min) 3 AT 80° C. 2% + 2% (20 min) 750.67 4 AV 80° C. 2% + 2% (20 min) + 52 1.5 2% (60 min) 5 AW 80° C. 2% +2% (20 min) + 50 1.5 2% (60 min)

Synthesis of (1aR,6R,7aS,15aS,Z)-methyl9-methyl-6-(4-nitrobenzoyloxy)-3,8-dioxo-1a,2,3,5,6,7,7a,8,9,10,11,12,13,15a-tetradecahydro-1H-cyclopropa[m]pyrrolo[1,2-c][1,3,6]triazacyclotetradecine-1a-carboxylateBJ. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.24 (t, J=7.1 Hz, 3H), 1.27-1.35(m, 1H), 1.37-1.47 (m, 1H), 1.49-1.62 (m, 1H), 1.66-1.79 (m, 3H), 1.87(br t, J=13.2 Hz, 1H), 2.26-2.47 (m, 2H), 2.60 (br d, J=13.5 Hz, 1H),3.05 (s, 3H), 3.51 (d, J=9.3 Hz, 1H), 3.94 (dd, J=9.8 and 5.3 Hz, 1H),4.06-4.16 (m, 1H), 4.18-4.27 (m, 1H), 4.57 (td, J=13.2 and 3.0 Hz, 1H),5.00 (s, 3H), 5.00-5.05 (m, 1H), 5.48 (t, J=10.3 Hz, 1H), 5.60-5.68 (m,1H), 5.72 (br s, 1H), 8.20 (d, J=8.8 Hz, 2H), 8.31 (d, J=8.8 Hz, 2H).

Synthesis of (1aR,6S,7aS,15aS,Z)-methyl6-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)-9-methyl-3,8-dioxo-1a,2,3,5,6,7,7a,8,9,10,11,12,13,15a-tetradecahydro-1H-cyclopropa[m]pyrrolo[1,2-c][1,3,6]triazacyclotetradecine-1a-carboxylateBL. ¹H NMR (CDCl₃, 400 MHz): δ (ppm) 1.29-1.44 (m, 2H), 1.50-1.62 (m,2H), 1.66 (s, 1H), 1.68-1.78 (m, 2H), 1.88 (td, J=13.5 and 2.5 Hz, 1H),2.15-2.23 (m, 1H), 2.40 (dd, J=9.9 and 9.5 Hz, 1H), 2.58 (td, J=13.7 and3.5 Hz, 1H), 2.68 (s, 3H), 2.97 (td, J=13.3 and 8.4 Hz, 1H), 3.04 (s,3H), 3.74 (s, 3H), 3.74-3.80 (m, 1H), 3.99 (s, 3H), 4.07 (t, J=7.5 Hz,1H), 4.62 (td, J=13.4 and 2.9 Hz, 1H), 4.95 (br t, J=6.7 Hz, 1H), 5.07(s, 1H), 5.41-5.53 (m, 2H), 5.65 (s, J=5.4 Hz, 1H), 7.25 (d, J=9.1 Hz,1H), 7.51 (s, 1H), 7.87 (s, 1H), 8.02 (d, J=9.1 Hz, 1H); MS (ESI, EE):m/z=687.98 (MH⁺).

TABLE 6 Compound BL Cata- Temp. Isolated Time Entry lyst (° C..)Catalyst loading yield (%) (hrs) 1 AO 80 2% + 2% (1 hr) + 2% (2 hrs) 512.5 2 AP 80 2% + 2% (1 hr) + 2% (2 hrs) 49 3 3 AQ 80 2% + 2% (1 hr) + 2%(2 hrs) 49 2.5 4 AR 80 2% + 2% (1 hr) + 2% (2 hrs) 48 2.5 5 AS 80 2% +2% (1 hr) + 2% (2 hrs) 49 2.5 6 AT 80 2% + 2% (1 hr) + 2% (2 hrs) 49 3 7AU 80 2% + 2% (1 hr) + 2% (2 hrs) 43 3.5 8 C5 80 2% + 2% (1 hr) + 2% (2hrs) 47 3 9 D4 80 2% + 2% (1 hr) + 2% (2 hrs) 38 3 10 E6 80 2% + 2% (1hr) + 2% (2 hrs) 42 3 11 G2 80 2% + 2% (1 hr) + 2% (2 hrs) 6 3.5

Synthesis of(Z)-(4R,6S,15S,17S)-[17-[7-methoxy-8-methyl-2-(4-trifluoromethylhiazol-2-yl)quinolin-4-yloxy]-13-N-methyl-2,14-dioxo-1,3,13-triazatricyclo[13.3.0.0]octadec-7-en-4-yl]carbonyl(1-methylcyclopropyl)sulfonamide68b. ¹H NMR (CDCl₁, 400 MHz): δ (ppm) 0.737 (m, 2H), 1.10-1.21 (m, 2H),1.26-1.33 (m, 2H), 1.44 (s, 3H), 1.41-1.53 (m, 1H), 1.56-1.65 (m, 1H),1.71-1.76 (m, 1H), 1.84 (dd, J=6.2 and 8.1 Hz, 2H), 2.11 (dt, J=5.7 and13.5 Hz, 1H), 2.36 (dd, J=9.3 and 18.9 Hz, 1H), 2.53 (dd, J=3.0 and 13.5Hz, 1H), 2.61 (s, 3H), 2.81 (ddd, J=4.7, 12.4 and 17.1 Hz, 1H),2.90-2.96 (m, 1H), 2.98 (s, 3H), 3.73 (dd, J=7.0 and 8.3 Hz, 1H), 3.92(s, 3H), 3.96 (t, J=7.7, 1H), 4.54 (dd, f=2.6 and 13.7 Hz, 1H), 4.84 (t,J=10.7 Hz, 1H), 4.89 (dd, J=5.3 and 8.9 Hz, 1H), 5.10 (s, 1H), 5.41 (q,J=7.0 Hz, 1H), 5.56 (td, J=5.8 and 10.8 Hz, 1H), 7.18 (d, J=9.2 Hz, 1H),7.42 (s, 1H), 7.80 (s, 1H), 7.94 (d, J=9.2 Hz, 1H), 11.12 (s, 1H); MS(ESI, Er) m/z=791 (MH⁺); MS (ESI, EI⁺) m/z m/z=791 (MH⁺).

TABLE 7 Compound 68b Temp. Isolated Time Entry Cat. (° C.) Catalystloading yield (%) (hrs) 1 AO 75 2% + 2% (45 min) + 2% (2 hrs) 75 4.0 2AP 60 2% + 2% (45 min) + 2% (2 hrs) + 2% (3 hrs) 45 24.0 3 AQ 60 2% + 2%(45 min) + 2% (2 hrs) + 2% (3 hrs) 63 24.0 4 AR 60 2% + 2% (45 min) + 2%(2 hrs) + 2% (3 hrs) 30 24.0 5 AS 60 2% + 2% (45 min) + 2% (2 hrs) + 2%(3 hrs) 60 24.0 6 AT 60 2% + 2% (45 min) + 2% (2 hrs) + 2% (3 hrs) 5324.0 7 C5 75 2% + 2% (45 min) + 2% (2 hrs) 70 4 8 D4 75 2% + 2% (45min) + 2% (2 hrs) 77 4 9 E6 75 2% + 2% (45 min) + 2% (2 hrs) 70 4 10 G275 2% + 2% (45 min) + 2% (2 hrs) 12 4

The examples set forth above are provided to give those of ordinaryskill in the art with a complete disclosure and description of how tomake and use the claimed embodiments, and are not intended to limit thescope of what is disclosed herein. Modifications that are obvious topersons of skill in the art are intended to be within the scope of thefollowing claims. All publications, patents, and patent applicationscited in this specification are incorporated herein by reference as ifeach such publication, patent or patent application were specificallyand individually indicated to be incorporated herein by reference.

1. A ruthenium complex of Formula I:

wherein: L is a neutral ligand; R¹ is C₁₋₁₂ alkyl, C₃₋₁₀ cycloalkyl,C₆₋₁₄ aryl, heteroaryl, heterocyclyl, or —NR^(3b)R^(3c); R² is H, C₁₋₁₂alkyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl; R³ is halo, cyano, nitro, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,heteroaryl, heterocyclyl, —C(O)R^(3a), —C(O)OR^(3a), —C(O)NR^(3b)R^(3c),—OR^(3a), —NR^(3b)R^(3c), —NR^(3a)C(O)R^(3b), —NR^(3a)C(O)OR^(3b),—NR^(3a)S(O)₂R^(3b), —PR^(3a)R^(3b), —P(OR^(3a))R^(3b),—P(OR^(3a))(OR^(3b)), —P(O)R^(3a)R^(3b), —P(O)(OR^(3a))R^(3b),—P(O)(OR^(3a))(OR^(3b)),—S(O)₂R^(3a), or —SO₂NR^(3b)R^(3c), R⁴ is C₁₋₁₂alkyl, C₃₋₁₀ cycloalkyl, C₇₋₁₅ aralkyl, or—C(R^(4a)R^(4b))C(O)NR^(4c)R^(4d); R⁵ is hydrogen, C₁₋₁₂ alkyl, C₂₋₁₂alkenyl, C₂₋₁₂ alkynyl, C₃₋₁₀ cycloalkyl, or C₆₋₁₄ aryl; each R^(3a) andR^(3d) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, or heterocyclyl; eachR^(3b) and R^(3c) is independently hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, heteroaryl, or heterocyclyl;or R^(3b) and R^(3c) together with the N atom form a heteroaryl orheterocyclyl; R^(4a) and R^(4b) are each independently hydrogen, C₁₋₆alkyl, C₃₋₈ cycloalkyl, C₆₋₁₄ aryl, or C₇₋₁₅ aralkyl; R^(4c) and R^(4d)are each independently hydrogen, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, C₆₋₁₄aryl, or C₇₋₁₅ aralkyl; or R^(4c) and R^(4d) together with the N atomform heterocyclyl; X¹ and X² are each independently an anionic ligand; Yis a bond or —NR^(b)—; Z is O or S; and n is an integer of 0, 1, 2, or3; wherein each alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl,heterocyclyl, and heteroaryl is optionally substituted with one or moregroups, each independently selected from (a) cyano, halo, or nitro; (b)C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl, each optionally substitutedwith one or more substituents Q; or (c) —C(O)R^(a), —C(O)OR^(a),—C(O)NR^(b)R^(c), —C(NR^(a))NR^(b)R^(c), —OR^(a), —OC(O)R^(a),—OC(O)OR^(a), —OC(O)NR^(b)R^(c), —OC(═NR^(a))NR^(b)R^(c), —OS(O)R^(a),—OS(O)₂R^(a), —OS(O)NR^(b)R^(c), —OS(O)₂NR^(b)R^(c), —NR^(b)R^(c),—NR^(a)C(O)R^(d), —NR^(a)C(O)OR^(d), —NR^(a)C(O)NR^(b)R^(c),—NR^(a)C(═NR^(d))NR^(b)R^(c), —NR^(a)S(O)R^(d), —NR^(a)S(O)₂R^(d),—NR^(a)S(O)NR^(b)R^(c), —NR^(a)S(O)₂NR^(b)R^(c), —PR^(a)R^(d),—P(OR^(a))R^(d), —P(OR^(a))(OR^(d)), —P(O)R^(a)R^(d),—P(O)(OR^(a))R^(d), —P(O)(OR^(a))(OR^(d)), —SR^(a), —S(O)R^(a),—S(O)₂R^(a), or —SO₂NR^(b)R^(c); wherein each R^(a), R^(b), R^(c), andR^(d) is independently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl,each optionally substituted with one or more substituents Q; or R^(b)and R^(c) together with the N atom to which they are attached formheterocyclyl, optionally substituted with one or more substituents Q;wherein each Q is independently selected from the group consisting of(i) cyano, halo, or nitro; (ii) C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₃₋₇ cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl;or (iii) —C(O)R^(e), —C(O)OR^(e), —C(O)NR^(f)R^(g),—C(NR^(e))NR^(f)R^(g), —OR^(e), —OC(O)R^(e), —OC(O)OR^(e),—OC(O)NR^(f)R^(g), —OC(═NR^(e))NR^(f)R^(g), —OS(O)R^(e), —OS(O)₂R^(e),—OS(O)NR^(f)R^(g), —OS(O)₂NR^(f)R^(g), —NR^(f)R^(g), —NR^(e)C(O)R^(h),—NR^(e)C(O)OR^(h), —NR^(e)C(O)NR^(f)R^(g), —NR^(e)C(═NR^(h))NR^(f)R^(g),—NR^(e)S(O)R^(h), —NR^(e)S(O)₂R^(h), —NR^(e)S(O)NR^(f)R^(g),—NR^(e)S(O)₂NR^(f)R^(g), —PR^(e)R^(h), —P(OR^(e))R^(h),—P(OR^(e))(OR^(h)), —P(O)R^(e)R^(h), —P(O)(OR^(e))R^(h),—P(O)(OR^(e))(OR^(h)), —SR^(e), —S(O)R^(e), —S(O)₂R^(e), or—S(O)₂NR^(f)R^(g); wherein each R^(e), R^(f), R^(g), and R^(h) isindependently hydrogen; C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₆₋₁₄ aryl, C₇₋₁₅ aralkyl, heteroaryl, or heterocyclyl; orR^(f) and R^(g) together with the N atom to which they are attached formheterocyclyl.
 2. The ruthenium complex of claim 1 having Formula Ia:


3. The ruthenium complex of claim 1 having Formula Ib:


4. The ruthenium complex of claim 1 having Formula Ic:


5. The ruthenium complex of claim 1, wherein L is a heterocyclic carbeneor phosphine, wherein the heterocyclic carbene is optionally substitutedwith one or more substituents.
 6. The ruthenium complex of claim 5,wherein the heterocyclic carbene is selected from the group consistingof:

wherein: each R¹¹ and R¹² is independently C₁₋₆ alkyl or C₆₋₁₄ aryl; andeach R¹³, R¹⁴, R¹⁵, and R¹⁶ is independently hydrogen, cyano, nitro,C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇ cycloalkyl, C₆₋₁₄ aryl,heteroaryl, or heterocyclyl; wherein each alkyl, alkenyl, alkynyl, aryl,cycloalkyl, heterocyclyl, and heteroaryl is optionally substituted withone or more substituents.
 7. The ruthenium complex of claim 6, whereinR¹³ or R¹⁵ is hydrogen or methyl.
 8. The ruthenium complex of claim 6,wherein R¹⁴ or R¹⁶ is hydrogen or methyl.
 9. The ruthenium complex ofclaim 6, wherein R¹¹ is C₆₋₁₄ aryl.
 10. The ruthenium complex of claim6, wherein R¹¹ is C₆₋₁₄ aryl, substituted with one or more C₁₋₆ alkyl.11. The ruthenium complex of claim 10, wherein R¹¹ is 2-methylphenyl,2,4,6-trimethylphenyl, or 2,6-di(isopropyl)phenyl.
 12. The rutheniumcomplex of claim 6, wherein R¹² is C₆₋₁₄ aryl.
 13. The ruthenium complexof claim 6, wherein R¹² is C₆₋₁₄ aryl, substituted with one or more C₁₋₆alkyl.
 14. The ruthenium complex of claim 13, wherein R¹² is2-methylphenyl, 2,4,6-trimethylphenyl, or 2,6-di(isopropyl)phenyl. 15.The ruthenium complex of claim 6, wherein the heterocyclic carbene isselected from the group consisting of:


16. The ruthenium complex of claim 5, wherein the phosphine isPR¹⁷R¹⁸R¹⁹, wherein R¹⁷, R¹⁸, and R¹⁹ are each independently C₁₋₁₂ alkylor C₆₋₁₄ aryl, each optionally substituted with one or moresubstituents.
 17. The ruthenium complex of claim 16, wherein R¹⁷ isphenyl or cyclohexyl.
 18. The ruthenium complex of claim 16, wherein R¹⁸is phenyl or cyclohexyl.
 19. The ruthenium complex of claim 16, whereinR¹⁹ is phenyl or cyclohexyl.
 20. The ruthenium complex of claim 16,wherein the phosphine is triphenylphosphine or tricyclohexylphosphine.21. The ruthenium complex of claim 1, wherein X¹ is halide, —C(O)R^(X),or —OC(O)R^(X), wherein R^(x) is alkyl, optionally substituted with oneor more halides.
 22. The ruthenium complex of claim 21, wherein X¹ ischloride.
 23. The ruthenium complex of claim 1, wherein X² is halide,—C(O)R^(X), or —OC(O)R^(X), wherein R^(x) is alkyl, optionallysubstituted with one or more halides.
 24. The ruthenium complex of claim23, wherein X² is chloride.
 25. The ruthenium complex of claim 1,wherein R¹ is C₁₋₅ alkyl, C₅₋₆ cycloalkyl, C₆₋₁₄ aryl, heteroaryl,heterocyclyl, or —NR^(3b)R^(3c).
 26. The ruthenium complex of claim 25,wherein R¹ is trifluoromethyl, phenyl, cyanophenyl, fluorophenyl,difluorophenyl, trifluoromethylphenyl, bis(trifluoromethyl)phenyl,trifluoromethylsulfonylphenyl, trifluoroacetylphenyl, nitrophenyl,dinitrophenyl, trifluoroacetamidophenyl, methoxyphenyl,pentofluorophenyl, pyridyl, trifluoromethyl-thiazolyl,trifluoromethyl-pyrazolyl, or dimethylamino.
 27. The ruthenium complexof claim 25, wherein R¹ is phenyl, 4-cyanophenyl, 4-fluorophenyl,3,5-difluorophenyl, 4-trifluoromethylphenyl),3,5-bis(trifluoromethyl)phenyl, 4-trifluoromethylsulfonylphenyl,4-trifluoroacetylphenyl, 4-nitrophenyl, 3,5-dinitrophenyl,4-trifluoroacetamidophenyl, 4-methoxyphenyl, pentofluorophenyl, pyridyl,4-trifluoromethylthiazolyl, or 3-trifluoromethyl-pyrazolyl, ordimethylamino.
 28. The ruthenium complex of claim 25, wherein R¹ isphenyl, 4-fluorophenyl, 3,5-difluorophenyl, 4-trifluoromethylphenyl,4-methoxyphenyl, or dimethylamino.
 29. The ruthenium complex of claim 1,wherein R² is C₁₋₅ alkyl or C₅₋₆ cycloalkyl.
 30. The ruthenium complexof claim 29, wherein R² is ethyl.
 31. The ruthenium complex of claim 1,wherein R³ is halo, cyano, nitro, —C(O)OR^(3a), —NR^(3a)S(O)₂R^(3b),—P(O)(OR^(3a))R^(3b), or —SO₂NR^(3b)R^(3c).
 32. The ruthenium complex ofclaim 1, wherein R⁴ is C₁₋₅ alkyl or C₅₋₆ cycloalkyl.
 33. The rutheniumcomplex of claim 32, wherein R⁴ is isopropyl.
 34. The ruthenium complexof claim 1, wherein R⁵ is hydrogen, C₁₋₅ alkyl, or C₅₋₆ cycloalkyl. 35.The ruthenium complex of claim 34, wherein R⁵ is hydrogen.
 36. Theruthenium complex of claim 1, wherein Z is O.
 37. The ruthenium complexof claim 1, wherein n is
 0. 38. The ruthenium complex of claim 1,wherein the complex is selected from the group consisting of:

wherein: Cmpd No. Y R¹ R¹¹ R¹² AP A bond

Mes Mes AQ A bond

Mes Mes AR A bond

Mes Mes AT A bond

Mes Mes C5 A bond —N(CH₃)₂ Mes Mes D4 A bond

Mes Mes E6 —NH—

Mes Mes G2 A bond

2-MePh 2-MePh.